Systematic investigation of CMTM family genes suggests relevance to glioblastoma pathogenesis and CMTM1 and CMTM3 as priority targets.
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.
Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
Sabit
S
Delic
Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
Andreas
A
Thuy
Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
Markus
M
Schulze
Department of Neurosurgery and, Regensburg University Hospital, Regensburg, Germany.|Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany.
Martin A
MA
Proescholdt
Institute of Biochemistry, Emil-FischerCenter, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany.
Peter
P
Dietrich
Institute of Biochemistry, Emil-FischerCenter, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany.
Anja-Katrin
AK
Bosserhoff
Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.|Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany.
Markus J
MJ
Riemenschneider
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D062792:MARVEL Domain-Containing Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D055815:Young Adult; D019061:src-Family Kinases / Q000378:metabolism
C515016:CMTM3 protein, human; C552173:CMTM7 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D051153:Wnt Proteins; D019061:src-Family Kinases