Exosomes are vital mediators for intercellular communications in the tumor microenvironment to accelerate colon cancer progression. Leucine-rich repeat-containing 8A (LRRC8A), the core component of the volume-regulated anion channel, is closely associated with acquiring heterogeneity for tumor cells. However, the role of LRRC8A in the exosomes remains largely unknown. Here, we reported that LRRC8A was one of the compositions in the exosomes released from colon cancer HCT116 cells. Down-regulation of LRRC8A proteins inhibited ex vivo cell growth and induced apoptosis. Consistently, chloride channel blockers DCPIB and NPPB inhibited cell growth and induced cell apoptosis in a time or concentration-dependent manner. Interestingly, the total amounts and proportions of different diameter exosomes released in 6 h were not altered by the treatment of DCPIB and NPPB in HCT116 cells. In contrast with the inhibition of LRRC8A, overexpression of LRRC8A proteins in HCT116 cells released significantly more distinct populations of exosomes. Importantly, the switches of ratios for exosomes in a hypotonic challenge were eliminated by DCPIB treatment. Collectively, our results uncovered that LRRC8A proteins were responsible for the exosome generation and sorted into exosomes for monitoring the volume regulation.
LRRC8A is responsible for exosome biogenesis and volume regulation in colon cancer cells
Haifeng Zhang, Shiyu Cui, Zhenghui Jing, Guodan Fu, Rong Liu, Wenbao Zhao, Liting Xu, Lei Yu, Yuhui Bai, Changsheng Lv, Min Wu, Yuan Wei, Liangming Li, Shuang Peng; LRRC8A is responsible for exosome biogenesis and volume regulation in colon cancer cells. Biochem J 17 May 2023; 480 (9): 701–713. doi: https://doi.org/10.1042/BCJ20220614
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