Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

RIPK1 binds MCU to mediate induction of mitochondrial Ca2+ uptake and promote colorectal oncogenesis (#321)

Fanxin Zeng 1
  1. Dazhou Central Hospital, Dazhou, SICHUAN, China


The receptor-interacting protein kinase 1 (RIPK1) is a critical signaling molecule in pathways for cell survival, apoptosis, and necroptosis. However, its role in colorectal cancer (CRC) remains elusive. Here we investigate the role of RIPK1 in human CRC carcinogenesis.


RIPK1 expression level was determined in patients CRC samples. Co-immunoprecipitation and a mass spectrum approach were used to detect RIPK1 interacting protein in human CRC samples, and human colon cancer cell line, HT 29 was also used for mechanistic study.


We found that RIPK1 was upregulated in human CRC tissues, and promoted cell proliferation when over expressed in HT29 cells. Mechanistically, RIPK1 interacted 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 its interaction with MCU and function in promoting cell proliferation.


These findings not only defined RIPK1 as a regulator of mitochondrial Ca2+ uptake, but also established RIPK1-mediated proliferation via MCU as a central mechanism underlying CRC progression. Suggest that RIPK1 and MCU are potential targets for CRC treatment.