Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma

Abstract

Endometrial carcinoma is a cancer derived from oncogenesis of the regenerating uterine cavity, in which cytokine stimulation shapes cell differentiation and tissue remodeling. Expression of the stem cell factors SOX2, OCT4, NANOG, and MYC has been linked to tumor malignancy in several cancers. However, how these stem cell factors crosstalk with cytokine signaling to promote malignancy in endometrial carcinoma is still elusive. Here we report that the expression of SOX2 and MYC, but not that of OCT4 and NANOG, correlate with poor histological differentiation and prognosis, while SOX2 expression is negatively associated with MYC level. We found that SOX2-high endometrial carcinoma cells possessed a higher colony-forming ability than their SOX2-low counterparts, and knockdown of SOX2 attenuated the colony-forming ability. We observed that SOX2 regulated EGFR expression in a SOX2–EGFR positive feedback loop. EGF stimulation induced SOX2 expression and promoted migration of endometrial carcinoma cells, whereas TGF-β stimulation inhibited SOX2 expression and attenuated the colony-forming ability. Immunohistochemistry analysis revealed that SOX2 expression correlated with lymph node infiltration of endometrial carcinoma. Our findings support that cytokine-induced stem cell factor SOX2 possesses oncogenic properties, with the potential to serve as a prognostic biomarker in endometrial carcinoma.

Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA

“…Third, our data demonstrated that the core stem gene SOX2 is the main target of HIF-dependent demethylase ALKBH5, which is involved in demethylation of downstream targets and further recruitment to m 6 A-modified sites. Our work in ECSCs revealed the relationship between HIFs and SOX2, which has been reported to be correlated with lymph node infiltration in EC 60 . In gastric cancer, SOX2 enhances HIF-1α promoter activity to regulate glucose metabolism 61 .…”

Tumor Evolution in a Patient with Recurrent Endometrial Cancer and Synchronous Neuroendocrine Cancer and Response to Checkpoint Inhibitor Treatment

“…In gastrointestinal [8] and lung [9] MiNENs, genetic and immunohistochemical studies have suggested a common origin in the amphicrine but not other subtypes. In our case, a crude comparison of significant variants that appeared in the neuroendocrine component shows emerging JAK1, PRKAR1A, and SOX9 mutations, some of which have been loosely associated with a neuroendocrine phenotype in early studies of multiple tumors but could also be tissue specific or random events [10–13]. It would take comparisons with multiple other similar tumors and considerations of the variants that disappeared in evolution to reach definite conclusions.…”

LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC

“…Then, we obtained 133 significantly up-regulated genes from the dataset GSE13003, which was intersected with the downstream transcription factors and finally MYC was obtained (Figures 4B, C). Previous evidence has demonstrated that high expression of MYC is related to low overall survival rate of EC patients (11). Therefore, we speculated that LINC00470 may regulate downstream pathways through MYC.…”

“…MYC is a known oncogene in human cancers, whereas its inhibition suppresses tumorigenesis (10). Furthermore, high expression of MYC may predict dismal overall survival rate of EC patients (11). Additionally, MYC can physically interact with DNA (cytosine-5)-methyltransferase 3a (DNMT3a), recruiting it to the promoter of microRNA-200b (miR-200b) to induce DNA hypermethylation (12).…”