Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India.
Cell Biol Int. 2022 Oct;46(10):1661-1671. doi: 10.1002/cbin.11853. Epub 2022 Jul 12.
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.
癌细胞与其肿瘤微环境的相互作用决定了疾病进展、治疗效果和耐药性发展的关键事件。在这里，我们提供的证据表明，他莫昔芬通过 AMPK 和 MAPK 信号通路调节线粒体动力学，在营养剥夺的情况下支持乳腺癌的生长。他莫昔芬通过抑制 Drp1 丝氨酸 616 磷酸化和上调 Mfn1 水平，在营养剥夺条件下增强线粒体融合。他莫昔芬诱导的线粒体融合是通过 AMPK 的激活介导的，这一点可以通过 AMPK 的药理学抑制逆转线粒体融合来证明。有趣的是，他莫昔芬通过 JNK 的激活来控制线粒体融合形态，通过下调 Mfn2 来控制。总的来说，他莫昔芬通过调节应激激酶信号在营养剥夺条件下增强线粒体融合来支持细胞生长。
