Congrats Dr. Dimpi Mukhopadhyay!!

Dr. Dimpi Mukhopadhyay has successfully defended her thesis on the Functional Role of the Calcium Channel TRPC6 in Breast Cancer Therapy Resistance and Metastasis. Dimpi will be continuing to expand her training and will be joining Dr. Evanna Mills lab at Dana Farber Cancer Institute for her postdoctoral research on immunometabolism. We are so proud of Dimpi and excited to see all she will achieve in her future!!

Photos of our celebration can be found on the Mercurio Lab Events page!

Our paper on YAP/TAZ- mediated regulation of laminin 332 promoting ferroptosis resistance is published in JBC!!

ABSTRACT

We are interested in the contribution of integrins and the extracellular matrix to epithelial differentiation in carcinomas. This study was motivated by our finding that the Hippo effectors YAP and TAZ can sustain the expression of laminin 332 (LM332), the predominant ECM ligand for the integrin β4, in breast carcinoma cells with epithelial differentiation. More specifically, we observed that YAP and TAZ regulate the transcription of the LAMC2 subunit of LM332. Given that the β4/LM332 axis is associated with epithelial differentiation and YAP/TAZ have been implicated in carcinoma de-differentiation, we sought to resolve this paradox. Here, we observed that the β4 integrin sustains the expression of miR-200s that target the transcription factor ZEB1 and that ZEB1 has a pivotal role in determining the nature of YAP/TAZ-mediated transcription. In the presence of β4, ZEB1 expression is repressed enabling YAP/TAZ/TEAD-mediated transcription of LAMC2. The absence of β4, however, induces ZEB1 and ZEB1 binds to the LAMC2 promoter to inhibit LAMC2 transcription. YAP/TAZ-mediated regulation of LAMC2 has important functional consequences because we provide evidence that LM332 enables carcinoma cells to resist ferroptosis in concert with the β4 integrin.

Goel HL, Karner ER, Kumar A, Mukhopadhyay D, Goel S, Mercurio AM. YAP/TAZ-mediated regulation of laminin 332 is enabled by β4 integrin repression of ZEB1 to promote ferroptosis resistance. Journal of Biological Chemistry. 2024 March 18. PMID: 38508310