Tumor suppressor CADM1 is involved in epithelial cell structure.
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.
Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Mika
M
Sakurai-Yageta
Mari
M
Masuda
Yumi
Y
Tsuboi
Akihiko
A
Ito
Yoshinori
Y
Murakami
D001798:Blood Proteins / Q000378:metabolism; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure*; D051528:Guanylate Kinases / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D001798:Blood Proteins; C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; C116869:DLG3 protein, human; C116887:EPB41L3 protein, human; D007136:Immunoglobulins; C089465:MPP1 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C496468:DLG2 protein, human; D051528:Guanylate Kinases