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Abstract: Santanu Dasgupta - Medical Biological Sciences

Understanding Cancer and Developing Early Detection Biomarkers

Abstract: Breast cancer or “carcinoma” develops generally from the epithelial cells through a multistep process called carcinogenesis. Lethality of these breast cancer cells is primarily due to the fact that these cells are able to invade, disseminate and form metastases throughout the body. One of the hallmarks of cancer cells is that they can adapt and survive under diverse micro-environmental stresses and inhibit normal epithelial cell differentiation. Another hallmark of these cancer cells is their ability to reprogram mitochondrial energy balance by altering their normal function. Mitochondria not only regarded as the powerhouse of the cell, but also involved in various cellular processes including cell death or apoptosis, growth, metabolism and differentiation. Mitochondria propagate through a process called fusion, through which damaged mitochondria fuse with the healthy ones and maintain a balance or homeostasis in the cell. Studies suggest that production of normal mitochondria in cancer cells could suppress tumor growth. My laboratory has recently uncovered a novel function of the mitochondrial fusion machinery in controlling breast cancer growth and their metastases. We found that restoration of mitochondrial fusion and the expression of its key regulator Mitofusin 2 (MFN2), reduce breast cancer growth and their spontaneous metastases. In further work, we discovered that defects in mitochondrial fusion can drive breast cancer growth and in this process, the breast cancer cell secreted exosomes play an important role through their unique ability of intercellular communication. These exosomes are small secreted cellular vesicles and carry the genetic information of the cancer cells. Transport of these exosomes to the neighboring cells can impact the growth of the cancer cells positively or negatively. In our study, we found that when the mitochondrial fusion factor MFN2 increased in the secreted exosomes of the breast cancer cells, fusion was normalized along with the reduction in breast cancer growth. This implicates for a functional link between mitochondrial fusion and their secreted exosomes through MFN2 in stopping breast cancer growth. From a translational viewpoint, our long-term objectives are to determine how mitochondrial fusion and their exosome related information is best exploited to stop breast cancer growth.

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