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Lee, Semin
Computational Biology Lab
Research Interests
  • Cancer genomics & single-cell genomics


Flightless-1 inhibits ER stress-induced apoptosis in colorectal cancer cells by regulating Ca2+ homeostasis

DC Field Value Language Choi, Sun Sil ko Lee, Sang Kwon ko Kim, Joong Kwan ko Park, Hye-Kyung ko Lee, Eujin ko Jang, Jinho ko Lee, Yo Han ko Khim, Keon Woo ko Hyun, Ji-Min ko Eom, Hye-jin ko Lee, Semin ko Kang, Byoung Heon ko Chae, Young Chan ko Myung, Kyungjae ko Myung, Seung-Jae ko Park, Chan Young ko Choi, Jang Hyun ko 2020-06-18T08:58:40Z - 2020-06-08 ko 2020-06 ko
dc.identifier.citation EXPERIMENTAL AND MOLECULAR MEDICINE, v.52, pp.940 - 950 ko
dc.identifier.issn 1226-3613 ko
dc.identifier.uri -
dc.description.abstract The endoplasmic reticulum (ER) stress response is an adaptive mechanism that is activated upon disruption of ER homeostasis and protects the cells against certain harmful environmental stimuli. However, critical and prolonged cell stress triggers cell death. In this study, we demonstrate that Flightless-1 (FliI) regulates ER stress-induced apoptosis in colon cancer cells by modulating Ca2+ homeostasis. FliI was highly expressed in both colon cell lines and colorectal cancer mouse models. In a mouse xenograft model using CT26 mouse colorectal cancer cells, tumor formation was slowed due to elevated levels of apoptosis in FliI-knockdown (FliI-KD) cells. FliI-KD cells treated with ER stress inducers, thapsigargin (TG), and tunicamycin exhibited activation of the unfolded protein response (UPR) and induction of UPR-related gene expression, which eventually triggered apoptosis. FliI-KD increased the intracellular Ca2+ concentration, and this upregulation was caused by accelerated ER-to-cytosolic efflux of Ca2+. The increase in intracellular Ca2+ concentration was significantly blocked by dantrolene and tetracaine, inhibitors of ryanodine receptors (RyRs). Dantrolene inhibited TG-induced ER stress and decreased the rate of apoptosis in FliI-KD CT26 cells. Finally, we found that knockdown of FliI decreased the levels of sorcin and ER Ca2+ and that TG-induced ER stress was recovered by overexpression of sorcin in FliI-KD cells. Taken together, these results suggest that FliI regulates sorcin expression, which modulates Ca2+ homeostasis in the ER through RyRs. Our findings reveal a novel mechanism by which FliI influences Ca2+ homeostasis and cell survival during ER stress. Cancer: Protein enhances survival of tumor cells under stress A cytoskeletal protein that helps tumors avoid cell death offers a promising new drug target for fighting cancer. A team led by Jang Hyun Choi and Sun Sil Choi of the Ulsan National Institute of Science and Technology, South Korea, detailed how a protein called Flightless I (FliI) that normally regulates the remodeling of structural filaments in the cell can, in colorectal cancer cells, serve as a tumor promoter through its action on calcium levels. Typically, cells respond to chronic stress by altering calcium signaling to promote their own death. In tumors, however, FliI maintains normal calcium levels to enhance cell survival even in the face of chemotherapy and other stressful stimuli. Suppressing FliI activity could thus help sensitize cancer cells to other stress- and death-inducing drug regimens. ko
dc.language 영어 ko
dc.title Flightless-1 inhibits ER stress-induced apoptosis in colorectal cancer cells by regulating Ca2+ homeostasis ko
dc.type ARTICLE ko
dc.identifier.scopusid 2-s2.0-85086020620 ko
dc.identifier.wosid 000538208500001 ko
dc.type.rims ART ko
dc.identifier.doi 10.1038/s12276-020-0448-3 ko
dc.identifier.url ko
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