breast cancer is one of the most prevalent malignancies in women, and its incidence is increasing significantly, particularly among younger populations (129). It is estimated that approximately one in eight women in developed countries will be diagnosed with breast cancer (130). In its early stages, breast cancer is often asymptomatic, leading to delayed diagnoses. Approximately 15% of patients are diagnosed with metastatic disease at initial presentation, which complicates timely treatment (131). Despite significant advances in therapeutic interventions, effectively managing metastatic breast cancer continues to be a challenge.

SATB1 has been identified as a key regulator in breast cancer progression and metastasis through its role in reprogramming gene expression networks (18, 23). The seminal study by Han et al. in 2008 laid the foundation for understanding SATB1’s involvement in breast cancer, showing that SATB1 mRNA and protein are predominantly expressed in metastatic breast cancer cell lines compared with non-malignant breast tissues. High levels of SATB1 expression were found to correlate with poor tumor differentiation and advanced disease stages (23). Zhang et al. further confirmed this finding, showing that SATB1 was abundantly expressed in breast cancer specimens but almost undetectable in normal and non-malignant tissues. Additionally, SATB1 expression gradually increased as breast tissues progressed from cystic hyperplasia to precancerous lesions, eventually reaching advanced breast cancer stages (91). Meanwhile, Kobierzycki et al. also reported a positive association between SATB1 expression and breast cancer progression, although their findings lacked statistical significance (132). These findings highlight its potential role in early cancer development.

Han et al. also reported that SATB1 promotes metastatic potential and invasiveness in breast cancer. They found that the ectopic expression of SATB1 in non-metastatic cells, inducing invasive behaviors and SATB1 knockdown in metastatic breast cancer cells (MDA-MB-231), reversed their invasive phenotype and prevented both lung metastases and primary tumor formation in mice (23). This gene expression analysis revealed that SATB1 modulates around 1,000 genes related to cell adhesion, signaling, and metastasis (23). However, a subsequent study by Iorns et al. using similar cell lines reported that SATB1 knockdown did not significantly affect invasiveness, and its overexpression failed to promote metastasis in non-invasive cells (133). Additionally, their clinical analysis showed no correlation between SATB1 expression and overall survival (OS) in patients with primary breast cancer (133). This inconsistency could be due to differences in cell line heterogeneity and RNA probe specificity (134). Further studies have reinforced the association between SATB1 and breast cancer aggressiveness. Wang et al. observed that SATB1 expression negatively correlated with TLR4 expression, which positively correlated with tumor size, stage, local lymph node metastasis, and estrogen receptor (ER) protein levels (135). Sun et al. found that SATB1 increased the breast cancer stem cell population within tumors and enhanced the expression of key EMT-related transcription factors, such as Snail and Twist1, further driving breast cancer metastasis (37). Additionally, Ma et al. revealed that the flavonoid baicalein effectively reduced breast cancer metastasis by inhibiting both SATB1 and the Wnt/β-catenin signaling pathway (22). This finding was further corroborated by Gao et al., who showed that baicalein suppressed breast cancer cell proliferation and migration by downregulating SATB1 (136). Notably, SATB1 was also found to act synergistically with HER2, an oncogene pivotal in breast cancer progression. SATB1 directly upregulated HER2 expression, thereby enhancing the tumorigenic potential of breast cancer cells (23, 92, 137). SATB1 is also regulated by non-coding RNAs, including miRNAs and long non-coding RNAs. Chen et al. identified SATB1 as a downstream effector gene of miR-409, revealing a negative correlation between the expression levels of these two genes. miR-409 was found to regulate the biological behavior of breast cancer cells by targeting SATB1. Furthermore, altering SATB1 levels could mitigate the effects of miR-409 on breast cancer cell proliferation and invasion (71). Additionally, SATB1 expression has been shown to positively correlate with H19, a long non-coding RNA that plays a crucial role in tumorigenesis (93, 138, 139). H19 sponges miRNA-130a-3p, resulting in SATB1 upregulation, thus promoting breast cancer progression (93) ( Figure 2 ). These studies highlight the multifaceted role of SATB1 in promoting breast cancer progression and metastasis.

The prognostic significance of SATB1 in breast cancer has been debated. Han et al. initially reported that high SATB1 expression was linked to poorer OS in patients with breast cancer (23). However, Hanker et al. observed no significant relationship between SATB1 expression and OS in ER-negative breast cancer, though it emerged as a positive prognostic marker in ER-positive cases (94). By contrast, Liu et al. identified SATB1 as an independent negative prognostic marker, with SATB1 positivity correlating with a significantly higher risk of poor outcomes (92). Laurinavicius et al. confirmed SATB1’s prognostic value, showing that a high Ki67/SATB1 ratio predicted worse OS in hormone-receptor-positive breast cancer (140). Nonetheless, conflicting results have emerged from other studies. For instance, Iorns et al. and Patani et al. found no significant association between SATB1 expression and patient outcomes (133, 141). Despite these conflicting results, a trend linking higher SATB1 expression to more aggressive disease and reduced OS persists. A 2016 meta-analysis by Pan et al. further validated SATB1’s role in breast cancer progression, associating its high expression with an advanced tumor stage, lymph node metastasis, and decreased survival rates (47). In summary, while inconsistencies exist in the literature, most evidence points to SATB1 as a key player in breast cancer progression and metastasis. Its potential role as a prognostic marker, particularly in predicting aggressive disease, warrants further investigation.

Ovarian cancer remains a leading cause of mortality among gynecological malignancies, primarily because of its metastatic potential and high recurrence rates. SATB1 overexpression has been observed in epithelial ovarian cancer, where it is positively associated with FIGO stages, lymph node metastasis, and poor prognosis (24, 29). SATB1 knockdown in ovarian cancer cells reduces lactate dehydrogenase (LDH) and monocarboxylate transporter 1 (MCT1) expression, key mediators of glucose metabolism. Simultaneously, tumor suppressor genes such as BRCA1 and BRCA2 are upregulated (95). These findings suggest that SATB1 may promote ovarian cancer metastasis by modulating cellular energy metabolism.

In lung cancer, particularly endometrial cancer, SATB1 expression is significantly higher in cancerous tissues than in non-cancerous tissues (96–98). It plays a critical role in promoting invasion and metastasis, in part through interactions with PAK5, a kinase involved in EMT regulation (98, 99). The PAK5-SATB1 axis may also play a critical role in the progression of other cancers. SATB1 expression in lung cancer correlates with tumor grade, infiltration depth, and lymph node metastasis (96, 97). Additionally, SATB1 has been identified as an independent negative prognostic marker in patients with endometrial cancer (97). In cervical cancer, high SATB1 expression is associated with poorer survival outcomes (142). While SATB1’s exact mechanisms in ovarian cancer and lung cancer progression remain under investigation, its role as a negative prognostic factor is well established.

prostate cancer is the second most common cause of cancer-related mortality among men worldwide (143). SATB1 has been identified as a key player in prostate cancer metastasis. Shukla et al. demonstrated that SATB1 expression significantly increases with advancing tumor grade (26). Mao et al. confirmed these findings, showing that SATB1 was expressed in prostate cancer tissues but was absent in benign prostatic hyperplasia. Moreover, SATB1 expression was positively correlated with the Gleason score, though it did not correlate with patient age or prostate-specific antigen levels, indicating its role in tumor progression rather than early detection (100).

Further research supports the critical role of SATB1 in maintaining the invasive potential of prostate cancer cells. Increased SATB1 expression has been positively correlated with enhanced cell invasiveness and migration (26, 100). In prostate cancer cell lines (PC-3M, DU-145, and LNCaP), SATB1 knockdown markedly reduces cell proliferation, invasion, and growth (26, 28, 100, 144). Moreover, SATB1 downregulation elevates CDH1 levels and reduces MMP-9 expression, reversing the EMT process and thereby restoring a more differentiated, less invasive phenotype (26). SATB1 knockdown in DU-145 cells also reduces cell viability, adhesion, and invasive capacity (28, 101–103). Conversely, SATB1 overexpression in LNCaP cells promotes xenograft tumor growth and induces EMT-related protein expression, further enhancing prostate cancer cell proliferation, invasion, and migration (102). Similarly, the transient transfection of SATB1 in PZ-HPV-7 cells increases their migratory and invasive capacities by 50–67%, along with downregulating CDH1 and upregulating MMP-9 (26). An innovative approach developed by Mao et al. utilized a lysosomal adenovirus vector carrying SATB1 shRNA (ZD55-SATB1), which selectively targets and replicates in DU-145 and LNCaP cells. This method significantly downregulated SATB1 expression, effectively reducing cell viability and invasion in vitro and in vivo (144). Overall, SATB1 consistently emerges as a promoter of proliferation, invasion, and migration in prostate cancer, while its downregulation triggers nuclear consolidation and apoptosis, particularly in DU-145 cells (102, 103). These findings highlight SATB1’s critical role in driving prostate cancer progression and its potential as a therapeutic target.

BLCA is ranked as the sixth most common cancer in men worldwide (143), and it has also been linked to SATB1 overexpression. SATB1 is highly expressed in both BLCA cell lines and clinical samples, with elevated levels correlating with shorter survival times for patients with BLCA (31, 105, 106). Loss- and gain-of-function studies have revealed that SATB1 plays a pivotal role in BLCA cell proliferation, migration, apoptosis, and sensitivity to cisplatin-based chemotherapy (31, 106). Notably, SATB1 promotes EMT in BLCA by downregulating CDH1 and upregulating key EMT-related transcription factors such as Snail, Slug, and Vimentin. This EMT activation enhances the invasive and metastatic capacities of BLCA cells. There is a strong inverse correlation between SATB1 and CDH1 expression at both the mRNA and protein levels, reinforcing SATB1’s role in promoting EMT and metastasis (31). Furthermore, SATB1 expression is positively correlated with critical clinical parameters, such as primary tumor invasion depth, lymph node metastasis, and TNM stages (31, 105). These associations underscore SATB1’s clinical relevance as a potential biomarker for aggressive disease and poor prognosis in patients with BLCA.

Research on SATB1 in lung cancer has primarily focused on NSCLC. Selinger et al. observed that, although SATB1 expression was significantly lower in NSCLC samples than in normal bronchial tissues, its expression varied by histological subtype. SATB1 expression was notably higher in SCC than in AC, where elevated levels were associated with poor differentiation and early-stage disease (108). In contrast, some studies have reported elevated SATB1 expression in AC tissues compared with adjacent non-malignant lung tissues (70, 90). These discrepancies likely reflect distinct SATB1 expression patterns across different lung tissues. SATB1 is generally highly expressed in the normal bronchial epithelium but nearly absent in alveolar cells (107). In NSCLC, SATB1 expression in AC is correlated with tumor hypo-differentiation, while in SCC, higher levels of SATB1 are found in well-differentiated tumors. Additionally, SATB1 expression has been positively associated with the proliferation marker Ki67 in SCC, though this correlation does not extend to AC (107). In the aggressive AC cell line A549, SATB1 knockdown significantly inhibits cell proliferation, migration, and invasion but promotes apoptosis, underscoring SATB1’s role in fostering a more aggressive tumor phenotype (90).

In 2021, Glatzel-Plucinska et al. explored the relationship between SATB1 expression and key EMT-related proteins in NSCLC clinical samples, observing strong positive correlations with EMT markers. Specifically, SATB1 showed a significant correlation with SLUG in SCC and Twist1 in AC, indicating its role in driving tumor progression via EMT in both subtypes (30, 90, 108). Further experiments revealed that SATB1 expression increased following EMT induction in NSCLC cell lines, such as A549 and NCI-H1703, supporting SATB1’s role as a positive regulator of EMT (32). Additionally, SATB1 knockdown in NSCLC cells downregulates tumor-promoting genes like c-myc, MMP2, MMP9, S100A4, and VEGF-B while also reducing the expression of EMT-related genes (e.g., N-cadherin, fibronectin) and inhibiting the Wnt/β-catenin pathway. Meanwhile, genes promoting apoptosis, such as Bcl-2, IL-2, and IL-2R, are upregulated (32, 36). By studying H1299, H358 and BEAS-2B cells and biochemical screening, Shalakha et al. determined that SATB1 is a novel HDAC5 substrate. HDAC5 deacetylates SATB1 at the conserved Lys 411 site. The dynamic acetylation at this site is determined by TIP60 acetyltrasferase. Significantly, HDAC5-mediated deacetylation is critical for SATB1-dependent downregulation of key tumor suppressor genes. HDAC5-SATB1 axis modulates the cellular transcriptional profile to promote tumor development (66). These findings indicate that SATB1 drives tumor growth and metastasis through multiple pathways, including the Wnt/β-catenin pathway, and its post-translational modifications could also be important to understand its role in tumorigenesis.

The prognostic role of SATB1 in NSCLC remains debated. Selinger et al. identified SATB1 deletion as a poor prognostic factor in SCC, but not in AC (108). Lower SATB1 levels have also been linked to shorter OS in patients with NSCLC and a history of smoking (108). However, Glatzel-Plucinska et al. reported that elevated SATB1 levels were a positive prognostic factor in NSCLC overall (AC and SCC combined), though the results were only marginally significant (107). These conflicting findings highlight the complexity of SATB1’s role in lung cancer and underscore the need for further research.

SATB1’s role in SCLC is less understood than that in NSCLC. SCLC is an aggressive cancer characterized by rapid growth and early metastasis. Despite its initial responsiveness to chemotherapy and radiotherapy, SCLC remains challenging to treat owing to frequent relapses (146). Selinger et al. reported higher SATB1 levels in SCLC samples compared with NSCLC, suggesting a different role for SATB1 in these subtypes (108). Interestingly, elevated SATB1 expression in SCLC was linked to better prognosis, although the small sample size limits the generalizability of these findings (108). Huang et al. further demonstrated higher SATB1 expression in SCLC tissues and metastatic lymph nodes than in adjacent normal tissues, reinforcing the idea that SATB1 contributes to SCLC progression (109). In the NCI-H446 SCLC cell line, SATB1 knockdown significantly inhibited proliferation and invasion while promoting apoptosis (109). In summary, SATB1 plays a multifaceted role in lung cancer, with its effects varying according to histological subtype. In NSCLC, SATB1 is implicated in EMT and tumor progression, while its role in SCLC, though less clear, also appears to promote aggressive cancer behavior. Although some findings suggest SATB1’s potential as a prognostic marker, further research is necessary to fully understand its clinical implications and therapeutic potential in both NSCLC and SCLC.

Despite advances in diagnostic and therapeutic strategies, the prognosis for advanced CRC remains poor, primarily because of its high metastatic potential (143). In 2011, Meng et al. demonstrated that SATB1 protein and mRNA were significantly overexpressed in CRC tissues, especially in patients with early-onset rectal cancer. Increased SATB1 levels correlated with higher metastatic potential and were significantly elevated in high-metastatic cells compared with low-metastatic ones (110). Subsequent studies have consistently confirmed that SATB1 is overexpressed in CRC samples relative to adjacent non-malignant tissues (32, 38, 111–115, 147, 148), with its overexpression associated with deeper tumor infiltration, lymph node metastasis, poor differentiation, and advanced TNM stages (32, 38, 110–112, 114, 115). Further studies also showed that the expression of SATB1 in lymph node metastasis was higher than that in primary lesion, and that in distant organ metastasis was higher than that in primary lesion (39). The increased expression of SATB1 correlates with expression profiles of various epigenetic factors including KDM6A, KDM6B and EMT factors Snail and ZEB1 suggesting a crosstalk between various EMT factors, SATB1 and epigenetic factors which drives the cancer towards metastasis associated (116).

SATB1’s role in CRC progression is partly attributed to its involvement in dysregulating the Wnt/β-catenin signaling pathway, which is critical for EMT in CRC. In normal colorectal mucosa, β-catenin is predominantly localized to cell membranes, but in CRC tissues with high SATB1 expression, β-catenin is found in the cytoplasm and nucleus. Luan et al. further confirmed that SATB1 induced β-catenin translocated into the nuclear and promotes colorectal cancer tumorigenesis by in vitro and in vivo experiments (39).This shift is associated with reduced membrane-bound β-catenin, increased EMT markers (e.g., Vimentin), and decreased CDH1 and CK20 levels, highlighting SATB1’s role in promoting metastasis (32). Furthermore, SATB1 not only acts as a target of the Wnt/β-catenin pathway but also regulates β-catenin expression (35). Wnt/β-catenin pathway hyperactivation induces SATB1 expression, which is repressed when TCF7L2 (TCF4) and β-catenin are depleted. SATB1, in turn, binds to the TCF7L2 promoter and modulates downstream Wnt signaling targets (35). Several studies have also shown that SATB1 knockdown in CRC cells reduces growth, migration, invasion, and colony formation while promoting apoptosis (38, 39, 110, 114, 115). SATB1 knockdown affects the expression of metastasis-related proteins, including CDH1, N-cadherin, Slug, Twist1, and MMP7, confirming its role in EMT and extracellular matrix degradation (33) ( Figure 3 ). In vivo studies further demonstrate that silencing SATB1 in LS174T cells injected into mice can significantly reduce tumor growth or even completely inhibit tumor formation (33). Conversely, SATB1 overexpression accelerates tumor growth and promotes metastasis to the liver and lungs (115).

The prognostic significance of SATB1 in CRC is controversial. While some studies suggest that SATB1 is an independent marker of poor prognosis (111–115), others have found no such association (147) or report prognostic value only in SATB2-negative tumors (24). Some studies even propose that high SATB1 expression may be associated with improved OS (149). Zhao et al. reported that high SATB1 expression is associated with shorter OS, low tumor differentiation, and distant metastasis but found no correlation between SATB1 and TNM stages (150). These findings suggest that further research is needed to clarify the mechanisms through which SATB1 impacts CRC prognosis, potentially related to its expression variants and the stage of cancer development.

Gastric cancer remains a leading cause of cancer-related deaths, especially in East Asia and Eastern Europe (143). SATB1 is significantly overexpressed in gastric cancer tissues compared with normal gastric mucosa (77, 117), with high SATB1 expression associated with poor survival, local invasion, lymph node metastasis, and advanced TNM stages (34, 117, 118, 151, 152). SATB1 overexpression is also linked to EMT promotion in gastric cancer, characterized by increased N-cadherin and Vimentin, along with reduced CDH1, correlating with advanced disease and lymph node metastasis (34). Furthermore, SATB1 has been implicated in the regulation of multidrug resistance (MDR) in gastric cancer, contributing to poor chemotherapy responses and worse outcomes (117, 118).

Long non-coding RNA UCA1 (lncRNA-UCA1) has emerged as a promising biomarker for early detection and prognostic prediction in gastric cancer, with elevated levels linked to poorer OS and disease-free survival (153). Additionally, miRNA-495-3p functions as a tumor suppressor in gastric cancer, where its loss leads to oncogene overexpression, promoting malignant transformation and tumor growth, while its overexpression inhibits tumor growth and metastasis (154, 155). Sun et al. explored the relationship between SATB1, miR-495-3p, and lncRNA-UCA1, revealing that SATB1 knockdown in gastric cancer cells inhibited cell proliferation and invasion, induced apoptosis, and mirrored the effects of miR-495-3p overexpression and lncRNA-UCA1 suppression (77). Their findings demonstrated that SATB1’s 3′-untranslated region (3′-UTR) and lncRNA-UCA1 competitively bind to miR-495-3p, with a luciferase reporter assay, confirming that miR-495-3p binds to multiple sites on SATB1’s 3′-UTR and a single site on lncRNA-UCA1 (77). SATB1 knockdown increased miR-495-3p binding to lncRNA-UCA1, reducing lncRNA-UCA1 expression. These results suggest that SATB1 3′-UTR functions as a competing endogenous RNA (ceRNA) for miR-495-3p, positively regulating lncRNA-UCA1. Interestingly, lncRNA-UCA1 knockdown reduced SATB1 expression in MKN-45 cells but not in BGC-823 cells (77), indicating a cell-dependent regulatory mechanism between lncRNA-UCA1 and SATB1 in gastric cancer. Similarly, LINC00491 accelerated head and neck squamous cell carcinoma progression through regulating miR-508-3p/SATB1 axis (156). Also, lncRNA IGF-like family member 2 antisense RNA 1 functioned as a ceRNA to sponge miR-1224-5p to regulate the expression of SATB1, regulating the Wnt/beta-catenin signaling pathway and tongue squamous cell carcinoma progression (157).

MDR remains a major challenge in treating gastric cancer, contributing to high mortality rates. Luo et al. found that high SATB1 expression in gastric cancer is associated with reduced sensitivity to various chemotherapeutic agents, promoting chemoresistance both in vitro and in vivo (119). SATB1 enhances the activity of ATP-binding cassette (ABC) transporter proteins—key players in reducing drug accumulation in cancer cells, thus promoting MDR—by altering their subcellular localization rather than expression (158). SATB1 also regulates the Ezrin promoter, which interacts with ABC transporters, contributing to chemoresistance (119). Receptor tyrosine kinases of the HER family, particularly HER2 and HER3, have been suggested to compensate for reduced MET function, contributing to resistance against MET inhibitors (159). SATB1 is implicated in the upregulation of HER3 expression following MET inhibition, enhancing HRG/HER3 signaling and thereby allowing gastric cancer cells to evade the cytotoxic effects of MET-targeted therapies (160). Additionally, SATB1 expression correlates positively with HER2, indicating a potential regulatory relationship between SATB1 and HER2 (117). Thus, targeting SATB1 offers a promising strategy for overcoming drug resistance in gastric cancer, potentially enhancing the effectiveness of chemotherapy. In conclusion, SATB1 plays a pivotal role in the progression, chemoresistance, and metastasis of gastric cancer, positioning it as a potential therapeutic target for improving treatment outcomes in patients with gastric cancer.

SATB1 has been closely linked to the progression of esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), the most common form of esophageal cancer, arising primarily from abnormal squamous epithelial cell proliferation (161). Studies have shown that SATB1 expression is significantly higher in ESCC tissues than in normal esophageal tissues, and its expression is strongly associated with TNM stages, though not with other clinicopathologic characteristics (120, 121). Importantly, patients with elevated SATB1 levels have significantly shorter survival times than those with lower SATB1 expression, making SATB1 a predictive marker for recurrence and poor prognosis in ESCC (120, 121).

Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses have identified fibronectin 1 (FN1) and platelet-derived growth factor receptor beta (PDGFRB) as key genes regulated by SATB1 in TE-1 cells (122). FN1 and PDGFRB are highly expressed in human esophageal cancer and play significant roles in promoting cell proliferation and migration. In other cancers, FN1 is known to stimulate the expression of matrix metalloproteinases, promoting invasion and metastasis (162), while PDGFRB supports the growth and survival of glioma stem cells (163) and breast cancer cell migration (164). Although the precise roles of these genes in esophageal cancer are not yet fully understood, their involvement in cancer progression is evident. A study by Song et al. revealed that SATB1 knockout in TE-1 and EC-109 cells significantly reduced the mRNA and protein levels of FN1 and PDGFRB (122). Moreover, a luciferase reporter assay confirmed that the activity of the FN1 and PDGFRB promoters increased approximately 2.5-fold following SATB1 transfection (122). These results suggest that SATB1 upregulates FN1 and PDGFRB, contributing to their oncogenic roles in ESCC by promoting cell survival and migration. Thus, SATB1 is a promising therapeutic target and prognostic marker in esophageal cancer.

Pancreatic cancer is one of the most lethal malignancies globally, with its incidence continuing to rise. SATB1 is overexpressed in pancreatic cancer, playing a critical role in promoting cancer cell proliferation and invasion. SATB1 expression is closely associated with tumor invasion depth and disease stage (58, 123). SATB1 knockdown has been shown to significantly inhibit cell proliferation, colony formation, and non-adherent growth while reducing the migratory capacity of pancreatic cancer cells in vitro. In vivo studies have also demonstrated that SATB1 downregulation suppresses tumor growth in xenograft models (123, 165). Additionally, elevated SATB1 expression is associated with shorter survival times in patients with pancreatic cancer (123, 124). Mechanistically, SATB1 binds to specific regions of the myc promoter, inducing myc mRNA expression, in turn promoting cancer cell growth, increasing the number of S-phase cells, and enhancing invasiveness in vitro. Conversely, SATB1 knockdown suppresses cancer cell proliferation and invasion (58). Blocking MYC in SATB1-overexpressing cells attenuates these effects, highlighting the SATB1–MYC axis as a potential therapeutic target (58). Recent research has also revealed that deleting deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2) reduces SATB1 expression, which regulates cyclin-dependent kinase 6 (CDK6), and directly controls cyclin-dependent kinase CDK1. This regulatory pathway leads to G1 phase arrest in MIA-PaCa-2 cells and G2 phase arrest in PK-1 cells, thereby inhibiting pancreatic cancer cell proliferation (166). These findings underscore the potential of SATB1 as a therapeutic target in pancreatic cancer.

Liver cancer is the third leading cause of cancer-related deaths worldwide (143). SATB1 is highly expressed in human hepatocellular carcinoma (HCC) tissues and in HCC cell lines with high metastatic potential, driving tumor growth in vivo (25). Clinical studies show that SATB1 expression correlates with larger tumor size, poor differentiation, and lymph node metastasis (25). Similarly, in intrahepatic cholangiocarcinoma, SATB1 expression has been associated with lymph node involvement and distant metastasis (167). In vitro studies further demonstrate that high SATB1 levels are associated with an aggressive cellular phenotype (25, 125). Research by Wei Tu et al. highlighted that SATB1 is strongly expressed in HCC cell lines with high metastatic potential, indicating a correlation between SATB1 expression and aggressive tumor behavior (126–128). Furthermore, SATB1 influences gene expression in HCC cells, regulating over 300 genes involved in tumor growth and metastasis (25). In vivo studies show that SATB1 promotes cell cycle progression by upregulating cyclin-dependent kinase 4 and downregulating p16INK4A, inhibiting apoptosis through the FADD–caspase-8–caspase-3 pathway. SATB1 also facilitates EMT, as evidenced by increased Snail1, Slug, Twist, and Vimentin expression and decreased CDH1, ZO-1, and desmoplakin expression (25). These findings suggest that SATB1 plays a critical role in HCC development by regulating key genes involved in cell cycle progression, apoptosis, and EMT, making it a potential therapeutic target in liver cancer.

Gene therapy has emerged as a promising treatment strategy for various diseases, particularly cancer, by targeting and modifying specific genes within cells. This approach offers significant advantages, including high specificity and minimal side effects, and, in some cases, holds the potential for a curative outcome (216, 217). However, a major challenge in gene therapy lies in the effective delivery of therapeutic genes. Delivery systems are generally categorized into viral and non-viral vectors, with non-viral vectors such as liposomes and nanoparticles gaining favor owing to their low immunogenicity.