Research Area
My interest is in understanding the signal interplay between metabolic adaptation and stress kinase signaling in cancer cells under different tumor micro-environment conditions. Identification of proteins that are associated with signaling cross-talk will help to determine the therapeutic potential of such interaction.
Our Lab Focus
Mitochondrial Dynamics
G-Protein Coupled Estrogen Receptor
Cell Migration and Actin Dynamics
Metabolic adaptations
Tamoxifen induces mitochondrial fusion during nutrition deprivation
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. Our recent work suggests that tamoxifen supports 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. 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 during nutrition deprivation.
Vijaykumar et al., Cell Biology International (2022)
https://doi.org/10.1002/cbin.11853
GPER induces mitochondrial fission through p44/42 MAPK - Drp1 pathway
Understanding GPER biology in breast cancer is rather limited in compassion to the classic estrogen receptors. Mitochondrial dynamics play a critical role in determining cell survival and death under various microenvironmental conditions. We present evidence that GPER-induce mitochondrial fission in breast cancer cells. GPER mediated mitochondrial fission through activating Drp1 by phosphorylating S616 residue and down-regulates fusion proteins Mfn1 and Mfn2 levels. GPER-induced Drp1 activation mediated by p44/42 MAPK and inhibition of this signalling axis completely reverse the mitochondrial fission induced by GPER. Further, mitochondrial fission is required for GPER-induced cell death in breast cancer cells. To conclude, GPER induces mitochondrial fission through p44/42 MAPK - Drp1 signalling, and mitochondrial fission is critical for GPER-induced cell death in breast cancer cells.
General significance: First time we report GPER's role in mitochondrial dynamics in cancer cells. Mitochondrial dynamics play a critical role in cancer progression including tamoxifen resistance. Exploring a detailed mechanistic understanding of GPER signalling may help to design new therapy for advanced cancers.
Rekha et al., Biochemical and Biophysical Research Communications 643 (2023) 16e23