TMEM180 contributes to colorectal cancer proliferation through intracellular metabolic pathways

TMEM180, a novel colon cancer specific membrane protein with a 12 transmembrane topology, is upregulated at low oxygen. Previously, we established a humanized monoclonal antibody against TMEM180 aimed at clinical trials. Prior to such trials, it is necessary to clarify the function of this molecule...

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Bibliographic Details
Published inbioRxiv
Main Authors Anzai, Takahiro, Saijou, Shinji, Ohnuki, Yoshitsugu, Kurosawa, Hiroshi, Yasunaga, Masahiro, Matsumura, Yasuhiro
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 17.07.2020
Subjects
Cell proliferation
Clinical trials
Colon cancer
Colorectal cancer
Colorectal carcinoma
Glucose metabolism
Glutamine
Glycolysis
Membrane proteins
Metabolic pathways
Metabolism
Metabolomics
Monoclonal antibodies
Next-generation sequencing
Nitric oxide
Oxygen consumption
Phosphorylation
Proteomics
Stockholders
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Summary:TMEM180, a novel colon cancer specific membrane protein with a 12 transmembrane topology, is upregulated at low oxygen. Previously, we established a humanized monoclonal antibody against TMEM180 aimed at clinical trials. Prior to such trials, it is necessary to clarify the function of this molecule in cancer. To compare SW480 human colon cancer cells and their TMEM180 knockdown derivatives, we analyzed proliferation and oxygen consumption, and also performed phosphorylation proteomics, metabolomics, and next-generation sequencing. The results revealed that TMEM180 promoted the growth of colon cancer but had almost no effect on oxygen consumption or expression of phosphorylated proteins. By contrast, glycolysis differed dramatically between SW480 and TMEM180 knockdown cells. TMEM180 promotes nitric oxide synthesis, suggesting that it promotes glucose metabolism and glutamine metabolism, thereby contributing to cancer growth. Overall, the results of this study support the clinical development of an anti TMEM180 antibody. Competing Interest Statement Y.M. is co-founder, shareholder, and Board Member of RIN Institute, Inc. S.S. is an employee of RIN Institute, Inc. M.Y. is a shareholder of RIN Institute, Inc. The other authors declare no competing interests.
DOI:10.1101/2020.07.16.207712