Interactome analysis reveals endocytosis and membrane recycling of EpCAM during differentiation of embryonic stem cells and carcinoma cells

Min Pan; Vera Kohlbauer; Alexandra Blancke Soares; Henrik Schinke; Yuanchi Huang; Gisela Kranz; Tanja Quadt; Matthias Hachmeister; Olivier Gires

doi:10.1016/j.isci.2021.103179

Interactome analysis reveals endocytosis and membrane recycling of EpCAM during differentiation of embryonic stem cells and carcinoma cells

iScience. 2021 Sep 27;24(10):103179. doi: 10.1016/j.isci.2021.103179. eCollection 2021 Oct 22.

Authors

Min Pan¹, Vera Kohlbauer², Alexandra Blancke Soares², Henrik Schinke², Yuanchi Huang², Gisela Kranz², Tanja Quadt², Matthias Hachmeister², Olivier Gires^{2

3}

Affiliations

¹ Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China.
² Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, LMU Munich, Munich, Germany.
³ Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer", Helmholtz Zentrum München, Neuherberg, Germany.

Abstract

Transmembrane epithelial cell adhesion molecule (EpCAM) is expressed in epithelia, carcinoma, teratoma, and embryonic stem cells (ESCs). EpCAM displays spatiotemporal patterning during embryogenesis, tissue morphogenesis, cell differentiation, and epithelial-to-mesenchymal transition (EMT) in carcinomas. Potential interactors of EpCAM were identified in murine F9 teratoma cells using a stable isotope labeling with amino acids in cell culture-based proteomic approach (n = 77, enrichment factor >3, p value ≤ 0.05). Kyoto Encyclopedia of Genes and Genomes and gene ontology terms revealed interactions with regulators of endosomal trafficking and membrane recycling, which were further validated for Rab5, Rab7, and Rab11. Endocytosis and membrane recycling of EpCAM were confirmed in mF9 cells, E14TG2α ESC, and Kyse30 carcinoma cells. Reduction of EpCAM during mesodermal differentiation and TGFβ-induced EMT correlated with enhanced endocytosis and block or reduction of recycling in ESCs and esophageal carcinoma cells. Hence, endocytosis and membrane recycling are means of regulation of EpCAM protein levels during differentiation of ESC and EMT induction in carcinoma cells.

Keywords: Cancer; Cell biology; Stem cells research.