Oncotarget

Research Papers:

HCaRG/COMMD5 inhibits ErbB receptor-driven renal cell carcinoma

Hiroyuki Matsuda, Carole G. Campion, Kyoko Fujiwara, Jin Ikeda, Suzanne Cossette, Thomas Verissimo, Maiko Ogasawara, Louis Gaboury, Kosuke Saito, Kenya Yamaguchi, Satoru Takahashi, Morito Endo, Noboru Fukuda, Masayoshi Soma, Pavel Hamet and Johanne Tremblay _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:69559-69576. https://doi.org/10.18632/oncotarget.18012

Metrics: PDF 1655 views  |   HTML 2740 views  |   ?  


Abstract

Hiroyuki Matsuda1,2,3, Carole G. Campion1, Kyoko Fujiwara3, Jin Ikeda3, Suzanne Cossette1, Thomas Verissimo1, Maiko Ogasawara3, Louis Gaboury4,5, Kosuke Saito3, Kenya Yamaguchi6, Satoru Takahashi6, Morito Endo7, Noboru Fukuda8, Masayoshi Soma3, Pavel Hamet1,2 and Johanne Tremblay1,2

1Centre de recherche, Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada, H2X 0A9

2Department of Medicine, Université de Montréal, Montréal, Québec, Canada, H3T 1J4

3Division of General Medicine, Department of Internal Medicine, Nihon University, Itabashi-ku, Tokyo, Japan, 173-8610

4Institut de Recherche en Immunologie et Cancérologie (IRIC), Université de Montréal, Pavillon Marcelle-Coutu, Québec, Canada, H3T 1J4

5Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec, Canada, H3T 1J4

6Department of Urology, Nihon University, Itabashi-ku, Tokyo, Japan, 173-8610

7Faculty of Human Health Science, Hachinohe Gakuin University, Hachinohe, Aomori, Japan, 031-8588

8University Research Center, Nihon University, Chiyoda-ku, Tokyo, Japan, 102-8251

Correspondence to:

Johanne Tremblay, email: [email protected]

Keywords: HCaRG/COMMD5, renal cell carcinoma, EGFR, differentiation, autophagic cell death

Received: March 10, 2017     Accepted: May 08, 2017     Published: May 19, 2017

ABSTRACT

Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death. Its overexpression in mouse renal cell carcinomas led to smaller tumor size with less tumor vascularization in a homograft tumor model. Mechanistically, HCaRG promotes de-phosphorylation of the proto-oncogene erythroblastosis oncogene B (ErbB)2/HER2 and epigenetic gene silencing of epidermal growth factor receptor and ErbB3 via promoter methylation. Extracellular signal-regulated kinase, AKT and mammalian target of rapamycin which mediate ErbB-dowstream signaling pathways are inactivated by HCaRG expression. In addition, HCaRG is underexpressed in human renal cell carcinomas and more expressed in normal tissue adjacent to renal cell carcinomas of patients with favorable prognosis. Taken together, our data suggest a role for HCaRG in the inhibition of tumor progression as a natural inhibitor of the ErbB signals in cancer and as a potential prognostic marker for renal cell carcinomas.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 18012