In:
Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-9-27)
Abstract:
One contributor to the high mortality of osteosarcoma is its reduced sensitivity to chemotherapy, but the mechanism involved is unclear. Improving the sensitivity of osteosarcoma to chemotherapy is urgently needed to improve patient survival. We found that chemotherapy triggered apoptosis of human osteosarcoma cells in vitro and in vivo ; this was accompanied by increased Sestrin2 expression. Importantly, autophagy was also enhanced with increased Sestrin2 expression. Based on this observation, we explored the potential role of Sestrin2 in autophagy of osteosarcoma. We found that Sestrin2 inhibited osteosarcoma cell apoptosis by promoting autophagy via inhibition of endoplasmic reticulum stress, and this process is closely related to the PERK-eIF2α-CHOP pathway. In addition, our study showed that low Sestrin2 expression can effectively reduce autophagy of human osteosarcoma cells after chemotherapy, increase p-mTOR expression, decrease Bcl-2 expression, promote osteosarcoma cell apoptosis, and slow down tumour progression in NU/NU mice. Sestrin2 activates autophagy by inhibiting mTOR via the PERK-eIF2α-CHOP pathway and inhibits apoptosis via Bcl-2. Therefore, our results explain one underlying mechanism of increasing the sensitivity of osteosarcoma to chemotherapy and suggest that Sestrin2 is a promising gene target.
Type of Medium:
Online Resource
ISSN:
2296-634X
DOI:
10.3389/fcell.2021.722960
DOI:
10.3389/fcell.2021.722960.s001
DOI:
10.3389/fcell.2021.722960.s002
DOI:
10.3389/fcell.2021.722960.s003
DOI:
10.3389/fcell.2021.722960.s004
DOI:
10.3389/fcell.2021.722960.s005
DOI:
10.3389/fcell.2021.722960.s006
DOI:
10.3389/fcell.2021.722960.s007
DOI:
10.3389/fcell.2021.722960.s008
DOI:
10.3389/fcell.2021.722960.s009
DOI:
10.3389/fcell.2021.722960.s010
DOI:
10.3389/fcell.2021.722960.s011
DOI:
10.3389/fcell.2021.722960.s012
DOI:
10.3389/fcell.2021.722960.s013
DOI:
10.3389/fcell.2021.722960.s014
DOI:
10.3389/fcell.2021.722960.s015
DOI:
10.3389/fcell.2021.722960.s016
DOI:
10.3389/fcell.2021.722960.s017
DOI:
10.3389/fcell.2021.722960.s018
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2737824-X
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