Autophagy and Cellular Senescence Mediated by Sox2 Suppress Malignancy of Cancer Cells

Abstract

Autophagy is a critical cellular process required for maintaining cellular homeostasis in health and disease states, but the molecular mechanisms and impact of autophagy on cancer is not fully understood. Here, we found that Sox2, a key transcription factor in the regulation of the “stemness” of embryonic stem cells and induced-pluripotent stem cells, strongly induced autophagic phenomena, including intracellular vacuole formation and lysosomal activation in colon cancer cells. The activation occurred through Sox2-mediated ATG10 gene expression and resulted in the inhibition of cell proliferation and anchorage-independent colony growth ex vivo and tumor growth in vivo. Further, we found that Sox2-induced-autophagy enhanced cellular senescence by up-regulating tumor suppressors or senescence factors, including p16INK4a, p21 and phosphorylated p53 (Ser15). Notably, knockdown of ATG10 in Sox2-expressing colon cancer cells restored cancer cell properties. Taken together, our results demonstrated that regulation of autophagy mediated by Sox2 is a mechanism-driven novel strategy to treat human colon cancers.

CD44, SHH and SOX2 as novel biomarkers in esophageal cancer patients treated with neoadjuvant chemoradiotherapy

“…This finding fits well with our previous observation that absence of SOX2 in EAC patients treated with surgery alone is related to poor survival in EAC patients [12]. A tumor-suppressor role of SOX2 is further supported by in vitro studies in gastric and colon cancer cells showing that overexpression of SOX2 has a tumor suppressor effect by reducing cell proliferation [25,26] and by a recent study that reported loss of SOX2 expression during progression of BE towards EAC and found this to be an independent predictive factor for malignant progression [27]. Taken together, low SOX2 expression might contribute to the development of EAC and a poor prognosis of EAC patients.…”

Physcion inhibits the metastatic potential of human colorectal cancer SW620 cells in vitro by suppressing the transcription factor SOX2

“…Consistent with these previous studies, evidence from the present study showed that physcion suppressed metastatic potential by downregulating SOX2 expression, thus supporting the promotional role of SOX2 in CRC metastasis. However, a subsequent study has identified that autophagy induced by SOX2 enhanced cellular senescence by upregulating tumor suppressors or senescence factors, including p16, p21 and phosphorylated p53 in colon adenocarcinoma cells [37] . Given the use of different CRC cell lines in the above study and different manipulation methods, the role of SOX2 in cancer progression or metastasis might depend on the specific cell type and is probably related to the constitutive expression level of SOX2.…”

Autophagy Protects Against Senescence and Apoptosis via the RAS-Mitochondria in High-Glucose-Induced Endothelial Cells

“…In contrast, beclin1, a major component of the autophagosome, combines with the anti-apoptotic Bcl-2 family to impair autophagy in senescent fibroblasts [9,10,11,31,32]. Beclin1 expression decreases in senescent cells and older tissues in parallel with an increase in the expression of the Bcl-2 family and a lower lysosomal uptake of binding substrates [33,34]. Thus, autophagy inhibition accelerates the development of senescence and apoptosis, although this theory is controversial [10].…”