RRC ID 64281
Author Funaki T, Ito T, Tanei ZI, Goto A, Niki T, Matsubara D, Murakami Y.
Title CADM1 promotes malignant features of small-cell lung cancer by recruiting 4.1R to the plasma membrane.
Journal Biochem Biophys Res Commun
Abstract Cell adhesion molecule 1 (CADM1), which mediates intercellular adhesion between epithelial cells, is shown to be highly expressed in small-cell lung cancer (SCLC) and to enhance tumorigenicity of SCLC cells in nude mice. Here, we investigated the molecular mechanism underlying the oncogenic role of CADM1 in SCLC. CADM1 promoted colony formation of SCLC cells in soft agar. Analysis of deletion and point mutants of the conserved protein-binding motifs in CADM1 revealed that the 4.1 protein-binding motif in the cytoplasmic domain is responsible for the promotion of colony formation. Among the actin-binding 4.1 proteins, 4.1R was the only protein whose localization to the plasma membrane is dependent on CADM1 expression in SCLC cells. Knockdown of 4.1R suppressed the colony formation enhanced by CADM1, suggesting that 4.1R is required for the oncogenic role of CADM1 in SCLC. In primary SCLC, CADM1 expression was correlated with membranous localization of 4.1R, as was observed in a SCLC cell line. Moreover, membranous co-localization of CADM1 and 4.1R was associated with more advanced tumor stage. These results suggest that the formation of CADM1-4.1R complex would promote malignant features of SCLC.
Volume 534
Pages 172-178
Published 2021-1-1
DOI 10.1016/j.bbrc.2020.11.121
PII S0006-291X(20)32165-3
PMID 33298314
MeSH Animals Cell Adhesion Molecule-1 / genetics Cell Adhesion Molecule-1 / metabolism* Cell Line, Tumor Cell Membrane / metabolism Cytoskeletal Proteins / metabolism* Female Lung Neoplasms / metabolism* Lung Neoplasms / pathology Membrane Proteins / metabolism* Mice, Inbred BALB C Mice, Nude Mutation Small Cell Lung Carcinoma / metabolism* Small Cell Lung Carcinoma / pathology
IF 2.985
DNA material pENTR4-H1 (RDB04395) CS-RfA-CG (RDB04390)