Silencing TFEB Suppresses Mammary Gland Acini Development and Proliferation

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Goyal, Ria

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Breast cancer is the most common type of cancer in the world. The aggressive and invasive nature of these tumors is explicable by the presence of cancer stem cells, which have self-renewal and initiation potentials that are analogous to the capabilities seen in normal mammary stem cells. The characterization of a protein’s role in a normal mammary gland, along with how this function is altered in cancerous tissue, enables enhanced understanding of the potential for specific novel drug targets. Transcription factor EB (TFEB) is currently known for its role as a master lysosomal regulator, and it has been shown to assist with cancerous progression through metabolic reprogramming. Yet, the key functions served by TFEB in mammary acini formation and its effects on mammary stem cells have never been determined. We have shown that the silencing of TFEB interrupts and disorganizes the development of mammary acini, unlike mere transcriptional inactivation. Furthermore, TFEB was not found to directly regulate the differentiation of mammary stem cells into a luminal lineage. Instead, TFEB appears to markedly contribute to the early proliferation of MCF10A cells, but additional investigation is necessary to characterize the mechanism. This work will guide future exploration into TFEB's potential as a drug target.


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