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Systematic investigation of CMTM family genes suggests relevance to glioblastoma pathogenesis and CMTM 1 and CMTM 3 as priority targets
Author(s) -
Delic Sabit,
Thuy Andreas,
Schulze Markus,
Proescholdt Martin A.,
Dietrich Peter,
Bosserhoff AnjaKatrin,
Riemenschneider Markus J.
Publication year - 2015
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22255
Subject(s) - downregulation and upregulation , wnt signaling pathway , biology , gene silencing , cancer research , gene , pathogenesis , rna interference , gene expression profiling , signal transduction , proto oncogene tyrosine protein kinase src , cell growth , gene expression , genetics , immunology , rna
The novel CKLF‐like Marvel Transmembrane Domain‐containing gene family (CMTM) consists of 8 members ( CMTM1–8 ). As little is known about the oncogenic impact of these genes, we aimed to systematically investigate the relevance of CMTMs to glioblastoma pathogenesis. We performed mRNA expression analyses and survival correlations in glioblastoma patients. Moreover, we analyzed the impact of RNAi‐based silencing and overexpression of CMTM family genes on tumor cell proliferation and invasion in vitro. CMTMs appeared to be widely regulated in the group of glioblastomas relative to non‐neoplastic brain (NB) tissue (significant upregulation for CMTM2 , 3 , and 6 and significant downregulation for CMTM 4 and 8 ). For CMTM1 , 5 and 7 , we found aberrant expression levels in individual tumors. Functionally, CMTM1 , 3 , and 7 promoted tumor cell invasion, while CMTM1 additionally enhanced cell proliferation. In a large clinically annotated dataset, higher CMTM1 and 3 expression was significantly correlated with shorter overall survival. Our data thus suggest CMTM1 and 3 as priority targets in glioblastomas. Using a human phosphokinase protein expression profiling assay, we can provide first insights into signalling of these two genes that might be conveyed by growth factor receptor, Src family kinase and WNT activation. © 2015 Wiley Periodicals, Inc.