RRC ID 19263
Author Sakurai-Yageta M, Masuda M, Tsuboi Y, Ito A, Murakami Y.
Title Tumor suppressor CADM1 is involved in epithelial cell structure.
Journal Biochem Biophys Res Commun
Abstract The tumor suppressor, CADM1, is involved in cell adhesion and preferentially inactivated in invasive cancer. We have previously reported that CADM1 associates with an actin-binding protein, 4.1B/DAL-1, and a scaffold protein, membrane protein palmitoylated 3 (MPP3)/DLG3. However, underlying mechanism of tumor suppression by CADM1 is not clarified yet. Here, we demonstrate that MPP1/p55 and MPP2/DLG2, as well as MPP3, interact with both CADM1 and 4.1B, forming a tripartite complex. We then examined cell biological roles of CADM1 and its complex in epithelia using HEK293 cells. Among MPP1-3, MPP2 is recruited to the CADM1-4.1B complex in the early process of adhesion in HEK293 cells. By suppression of CADM1 expression using siRNA, HEK293 lose epithelia-like structure and show flat morphology with immature cell adhesion. 4.1B and MPP2, as well as E-cadherin and ZO-1, are mislocalized from the membrane by depletion of CADM1 in HEK293. Mislocalization of MPP2 is also observed in several cancer cells lacking CADM1 expression with the transformed morphology. These findings suggest that CADM1 is involved in the formation of epithelia-like cell structure with 4.1B and MPP2, while loss of its function could cause morphological transformation of cancer cells.
Volume 390(3)
Pages 977-82
Published 2009-12-18
DOI 10.1016/j.bbrc.2009.10.088
PII S0006-291X(09)02079-8
PMID 19854157
MeSH Blood Proteins / metabolism Cell Adhesion Cell Adhesion Molecule-1 Cell Adhesion Molecules Cell Line, Tumor Epithelial Cells / metabolism Epithelial Cells / ultrastructure* Guanylate Kinases / metabolism Humans Immunoglobulins / genetics Immunoglobulins / metabolism* Lung Neoplasms / metabolism Lung Neoplasms / ultrastructure* Membrane Proteins / genetics Membrane Proteins / metabolism* Microfilament Proteins Nuclear Proteins / metabolism RNA, Small Interfering / genetics Transcription Factors / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*
IF 2.985
Times Cited 42
Human and Animal Cells COS-7(RCB0539)