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Cellular signalling

Cellular signalling

IF: 4.4
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Phosphorylated Hsp27 promotes adriamycin resistance in breast cancer cells through regulating dual phosphorylation of c-Myc

Published:4 October 2023 DOI: 10.1016/j.cellsig.2023.110913 PMID: 37797796
Xiaowen Bi , Miao Zhang , Jinyi Zhou , Xintong Yan , Lixia Cheng , Lan Luo , Chunhong Huang , Zhimin Yin

Abstract

Chemotherapy resistance of breast cancer cells is one of the major factors affecting patient survival rate. Heat shock protein 27 (Hsp27) is a member of the small heat shock protein family that has been reported to be associated with chemotherapy resistance in tumor cells, but the exact mechanism is not fully understood. Here, we explored the regulation of Hsp27 in adriamycin-resistant pathological conditions of breast cancer in vitro and in vivo. We found that overexpression of Hsp27 in MCF-7 breast cancer cells reversed DNA damage induced by adriamycin, and thereby reduced subsequent cell apoptosis. Non-phosphorylated Hsp27 accelerated ubiquitin-mediated degradation of c-Myc under normal physiological conditions. After stimulation with adriamycin, Hsp27 was phosphorylated and translocated from the cytoplasm into the nucleus, where phosphorylated Hsp27 upregulated c-Myc and Nijmegen breakage syndrome 1 (NBS1) protein levels thus leading to ATM activation. We further showed that phosphorylated Hsp27 promoted c-Myc nuclear import and stabilization by regulating T58/S62 phosphorylation of c-Myc through a protein phosphatase 2A (PP2A)-dependent mechanism. Collectively, the data presented in this study demonstrate that Hsp27, in its phosphorylation state, plays a critical role in adriamycin-resistant pathological conditions of breast cancer cells.

Substances (20)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
KU-55933 587871-26-9 C21H17NO3S2 182 suppliers $14.00-$3176.25
KU-55933 587871-26-9 C21H17NO3S2 182 suppliers $14.00-$3176.25
KU-55933 587871-26-9 C21H17NO3S2 182 suppliers $14.00-$3176.25
KU-55933 587871-26-9 C21H17NO3S2 182 suppliers $14.00-$3176.25
(Z,E)-5-(4-ETHYLBENZYLIDINE)-2-THIOXOTHIAZOLIDIN-4-ONE 403811-55-2 C12H11NOS2 154 suppliers $19.00-$1654.10
(Z,E)-5-(4-ETHYLBENZYLIDINE)-2-THIOXOTHIAZOLIDIN-4-ONE 403811-55-2 C12H11NOS2 154 suppliers $19.00-$1654.10

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