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Cancer Res. 2018 Jun 1;78(11):2876-2885. doi: 10.1158/0008-5472.CAN-17-3082. Epub 2018 Mar 12.

RIPK1 Binds MCU to Mediate Induction of Mitochondrial Ca2+ Uptake and Promotes Colorectal Oncogenesis.

Zeng F#1,2, Chen X#3, Cui W#1,2, Wen W1,2, Lu F1, Sun X1,2, Ma D1,2, Yuan Y1,2, Li Z1,2, Hou N1,2, Zhao H3, Bi X3, Zhao J3, Zhou J3, Zhang Y1,2,4, Xiao RP1,2,4, Cai J5, Zhang X6,2.

Author information

1
Institute of Molecular Medicine, Peking University, Beijing, China.
2
Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, China.
3
Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
4
State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking-Tsinghua Center for Life Sciences, Beijing, China.
5
Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. zhangxq@pku.edu.cn caijianqiang188@sina.com.
6
Institute of Molecular Medicine, Peking University, Beijing, China. zhangxq@pku.edu.cn caijianqiang188@sina.com.
#
Contributed equally

Abstract

The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation. These findings identify the RIPK1-MCU pathway as a promising target to treat colorectal cancer.Significance: RIPK1-mediated cell proliferation through MCU is a central mechanism underlying colorectal cancer progression and may prove to be an important therapeutic target for colorectal cancer treatment. Cancer Res; 78(11); 2876-85. ©2018 AACR.

PMID:
29531160
DOI:
10.1158/0008-5472.CAN-17-3082
[Indexed for MEDLINE]
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