Targeting copper metabolism to defeat KRAS-driven colorectal cancer

Léo Aubert; Neethi Nandagopal; Philippe P Roux

doi:10.1080/23723556.2020.1822123

Targeting copper metabolism to defeat KRAS-driven colorectal cancer

Mol Cell Oncol. 2020 Oct 7;7(6):1822123. doi: 10.1080/23723556.2020.1822123.

Authors

Léo Aubert¹, Neethi Nandagopal¹, Philippe P Roux^{1

2}

Affiliations

¹ Institute for Research in Immunology and Cancer (IRIC), Université De Montréal, Montreal, Quebec, Canada.
² Department of Pathology and Cell Biology, Faculty of Medicine, Université De Montréal, Montreal, Quebec, Canada.

Abstract

KRAS-driven cancers acquire profound metabolic dependencies that are intimately linked to tumor growth. Our work revealed that colorectal cancers that harbor KRAS mutations are addicted to copper metabolism. This adaptation renders tumor cells critically dependent on the copper transporter ATP7A, which reveals copper metabolism as a promising therapeutic target for KRAS-driven colorectal cancers.

Keywords: ATP7A; Copper; KRAS; TTM; chelators; colorectal cancer; micronutrients.

Grants and funding

Our work is funded by grants from the Canadian Institutes for Health Research (CIHR) and the Cancer Research Society (CRS). P.P.R. is a Senior Scholar of the Fonds de la recherche du Québec-Santé (FRQS). L.A. received a Postdoctoral Fellowship from the Cole Foundation, and N.N. was supported by Doctoral Scholarships from the FRQS and the Fonds de la recherche du Québec-Nature and Technologies (FRQNT).