Journal
CANCER RESEARCH
Volume 78, Issue 11, Pages 2876-2885Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-17-3082
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Funding
- National Natural Science Foundation of China [81471063, 81270883, 81672461]
- National Science and Technology Major Projects for Major New Drug Innovation and Development [2013ZX09501014]
- National Key Basic Research Program of China [2013CB531200, 2012CB518000]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001, 2017-12M-4-002]
- National High-tech R&D (863) Program of China [2015AA020408]
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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. (C) 2018 AACR.
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