Tamoxifen modulates mitochondrial dynamics through AMPK and MAPK during nutrition deprivation

Autor: Gangipangi Vijayakumar, Uppalapati S. Swetha, Selvaraju Sudhagar
Rok vydání: 2022
Předmět:
Zdroj: Cell Biology International. 46:1661-1671
ISSN: 1095-8355
1065-6995
DOI: 10.1002/cbin.11853
Popis: The interaction of cancer cells with their tumor microenvironment determines key events in the progression of the disease, therapeutic efficacy, and the development of drug resistance. Here, we presented evidence that tamoxifen support breast cancer growth during nutrition deprivation by modulating mitochondrial dynamics through AMPK and MAPK signaling. Tamoxifen enhances mitochondrial fusion under nutrition-deprived conditions by suppressing Drp1 ser616 phosphorylation and upregulating Mfn1 levels. Tamoxifen-induced mitochondrial fusion is mediated by the activation of AMPK as evident by the pharmacological inhibition of AMPK reverse mitochondrial fusion. Interestingly, JNK activation by tamoxifen controls the mitochondrial fusion morphology by downregulating Mfn2. Collectively, tamoxifen support cell growth by enhancing mitochondrial fusion by regulating stress kinase signaling under nutrition deprivation condition.
Databáze: OpenAIRE
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