The role of EpCAM in tumor progression and the clinical prognosis of endometrial carcinoma

Wen, Kuo Chang; Sung, Pi Lin; Chou, Yu‐Ting; Pan, Chih‐Ming; Wang, Peng Hui; Lee, Oscar K.; Wu, Cheng‐Wen

doi:10.1016/j.ygyno.2017.11.033

Cited by 31 publications

(20 citation statements)

References 39 publications

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“…99040201) and Ishikawa (Heraklio) 02 ER- cells (ECACC No. 98032302) were obtained from the European Collection of Authenticated Cell Cultures as described previously 43 . Ishikawa cells harbor estrogen receptors (ER+) and were originally established from an endometrial adenocarcinoma from a 39 year old woman with the ability to induce well differentiated adenocarcinoma in the xenograft nude mice model 44 .…”

Section: Methodsmentioning

confidence: 99%

Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma

Lee

Sung

Kuo

et al. 2018

Sci Rep

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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.

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Section: Methodsmentioning

confidence: 99%

Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma

Lee

Sung

Kuo

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another essential aspect is that cancer-related lethality is primarily caused by therapy-resistant cells and frequently untreatable metastases. Numerous studies on EpCAM's prognostic value have initially concentrated on primary tumors rather than disseminated cells [12,[57][58][59][60][61][62][63][64][65][67][68][69][70][71][72][73]. However, primary tumor biopsies represent a specific region of the tumor at a given time point.…”

Section: Epcam As a Prognostic Marker In Cancermentioning

confidence: 99%

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

Gires

Pan

Schinke

et al. 2020

Cancer Metastasis Rev

181

140

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EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.

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“…Gosens et al ( 113 ) observed that reduced EpCAM expression at the invasive margin of rectal carcinomas, and reduction of EpCAM expression may increase the risk of local recurrence. A recent report revealed that loss of EpCAM increases the malignancy of endometrial carcinoma (EC), and high EpCAM expression favors the survival of patients with EC ( 114 ). The molecular mechanisms of the tumor suppressive function of EpCAM in these cancers are not yet clear.…”

Section: Functions Of Epcam In Diseasesmentioning

confidence: 99%

Functions of EpCAM in physiological processes and diseases (Review)

et al. 2018

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EpCAM (epithelial cell adhesion molecule) is a type I transmembrane glycoprotein, which was originally identified as a tumor-associated antigen due to its high expression level in rapidly growing epithelial tumors. Germ line mutations of the human EpCAM gene have been indicated as the cause of congenital tufting enteropathy. Previous studies based on cell models have revealed that EpCAM contributes to various biological processes including cell adhesion, signaling, migration and proliferation. Due to the previous lack of genetic animal models, the in vivo functions of EpCAM remain largely unknown. However, EpCAM genetic animal models have recently been generated, and are useful for understanding the functions of EpCAM. The authors here briefly review the functions and mechanisms of EpCAM in physiological processes and different diseases.

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The role of EpCAM in tumor progression and the clinical prognosis of endometrial carcinoma

Cited by 31 publications

References 39 publications

Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma

Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?

Functions of EpCAM in physiological processes and diseases (Review)

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