SIX1 is upregulated in gastric cancer and regulates proliferation and invasion by targeting the ERK pathway and promoting epithelial‐mesenchymal transition

Abstract

Sine oculis homeobox homologue 1 (SIX1) is a Six class homeobox gene conserved throughout many species. It has been reported to act as an oncogene and is overexpressed in many cancers. However, the function and regulatory mechanism of SIX1 in gastric cancer (GC) remains unclear. In our study, we detected protein levels of SIX1 via immunohistochemistry (IHC) and its proliferation and invasion effects via CCK8 and transwell assays. Additionally, expression of cyclin D1, MMP2, p‐ERK, and EMT‐related proteins was measured by western blotting. We found that SIX1 had significantly higher expression in GC tissues and that it could promote GC cell proliferation and invasion. Also, overexpression of SIX1 increased the expression of cyclin D1, MMP2, p‐ERK, and EMT‐related proteins, which could all be inhibited by knocking down SIX1. In conclusion, SIX1 is upregulated in GC tissues. It can promote GC cell proliferation by targeting cyclin D1, invasion via ERK signalling, and EMT pathways by targeting MMP2 and E‐cadherin. Significance of the study Our study showed that SIX1 was upregulated in GC tissues, and promoted GC cell proliferation by targeting cyclin D1, invasion via ERK signalling, and EMT pathways by targeting MMP2 and E‐cadherin. These results suggested the potential regulatory mechanism of SIX1 in proliferation and invasion of gastric cancer.

Zonula occludens-1 associated nucleic acid binding protein plays an invasion-promoting role in bladder cancer

“…Since epithelial-mesenchymal transition (EMT) is required for cell invasion involved in cancer progression [24,25], we investigated the expression of EMT markers following ZONAB up-regulation and found that ZONAB can down-regulate the expression of cytokeratin 8 and up-regulate the expression of vimentin, which is consistent with the result of Jiménez-Salazar and his colleague's study in breast cancer [50]. Our ndings demonstrate that ZONAB expression enhances epithelial-mesenchymal transition in bladder cancer.…”

“…us, the negative inhibitory e ect of ZONAB on E-cadherin expression suggests that up-regulation of ZONAB in bladder cancer enhances the invasive phenotype of bladder cancer. Epithelial-mesenchymal transition (EMT) is required for cell invasion involved in cancer progression [24,25]. To identify EMT following ZONAB up-regulation in bladder cancer, the expression of cytokeratin 8 as an epithelial marker and vimentin as a mesenchymal marker in xenogra tumor was detected by immunohistochemical staining.…”

Integrated analysis of long non-coding RNAs and mRNA profiles reveals potential sex-dependent biomarkers of bevacizumab/erlotinib response in advanced lung cancer

“…In addition, ENST00000575695.5 primarily regulated UBQLN1, which is linked with hypoxia responses in cells. Previous studies have also explored the roles of G6PC3, ATF6, BMP2, SIX1, RAB7A, and SOX2 in tumors [42][43][44][45][46][47] Together our results most clearly highlighted the importance of TEK, LDB2, ATF6 and UBQLN1 in NSCLC patient BE responses, underscoring the value of examining system-level gene interactions in order to better understand the determinants of lung cancer patient therapeutic responsiveness.…”

miR-489-3p/SIX1 Axis Regulates Melanoma Proliferation and Glycolytic Potential

“…19 In gastric cancer cells, SIX1 inhibits the mitochondrial apoptosis pathway via caspase-7, and it regulates proliferation and invasion by targeting the ERK pathway. 20,21 Liu et al 22 showed that SIX1 promotes tumor lymphangiogenesis via coordinating transforming growth factor b (TGF-b) signals that increase expression of vascular endothelial growth factor C (VEGF-C). In breast cancer, SIX1 overexpression reinstates an embryonic pathway of proliferation by upregulating cyclin A1 21 and mediates resistance to paclitaxel in breast cancer cells.…”

“…20,21 Liu et al 22 showed that SIX1 promotes tumor lymphangiogenesis via coordinating transforming growth factor b (TGF-b) signals that increase expression of vascular endothelial growth factor C (VEGF-C). In breast cancer, SIX1 overexpression reinstates an embryonic pathway of proliferation by upregulating cyclin A1 21 and mediates resistance to paclitaxel in breast cancer cells. 22 Moreover, multiple studies have demonstrated that high SIX1 expression leads to poor survival in a variety of cancers.…”