20 Dec A Neuronal Network of Mitochondrial Dynamics Regulates Cancer Metastasis
MedicalResearch.com Interview with:
Cecilia Caino, Ph.D.
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Mitochondria have recently experienced a resurgence of interest in the field of cellular biology. Traditionally known for their role in energy production and in programmed cell death, mitochondria are more broadly recognized as signaling hubs and biosynthetic factories. Not surprisingly, mitochondria have been linked to several hallmarks of cancer, including evasion of apoptosis, tissue invasion and metastasis and abnormal metabolic pathways. It has become clear that mitochondria quality control and metabolism-regulated shape changes are dysregulated in cancer. Recent studies identified a novel therapy-resistance mechanism that involves mitochondrial subcellular re-localization and is responsible for enhanced metastatic potential of cancer cells. In this context, the molecular regulators of mitochondrial trafficking in cancer are largely unknown.
Through analysis of shRNA screening results, we identified Syntaphilin (SNPH), which is considered to moderate mitochondrial trafficking in neurons, as a non-neuronal tissue specific factor to suppress cancer cell invasion. Using multi-disciplinary cell biological, real time imaging, in vivo studies and human clinical studies, SNPH was revealed to block cell motility and tumor metastasis by regulation of reprogramming of mitochondrial dynamics. We provided evidence from public databases and clinical samples that SNPH levels are decreased in different types of human tumors and low SNPH levels correlate with worse patient prognosis. Overall this study demonstrated a new mechanism by which tumor cell invasion is regulated by a SNPH-mediated pathway.
MedicalResearch.com: What should readers take away from your report?
Response: SNPH is a key molecule that regulates mitochondrial motility in cancer cells, this impacts on cancer cell invasion and metastasis and ultimately on patient survival.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The processes of mitochondrial trafficking and dynamics might provide viable therapeutic targets to prevent disease dissemination. These are relatively novel pathways in cancer biology, and much research needs to be done to get a comprehensive picture of how these pathways are wired, how do they transduce cellular stress and ultimately which are the best potential targets for molecular therapy.
MedicalResearch.com: Is there anything else you would like to add?
Response: There has been an incredible progress in mitochondria biology during the past decade and as a result now we know more about mitochondria in health and disease. We are grateful to our colleagues that did much of the legwork to identify the mechanism of mitochondrial movement via motor proteins in neurons and other normal cell types. Their work was essential to put our findings in cancer cells into the context of why and how this pathway might be spatiotemporally regulated to fuel metastasis.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
A neuronal network of mitochondrial dynamics regulates metastasis
M. Cecilia Caino, Jae Ho Seo, Angeline Aguinaldo, Eric Wait, Kelly G. Bryant, Andrew V. Kossenkov,James E. Hayden, Valentina Vaira, Annamaria Morotti, Stefano Ferrero, Silvano Bosari, Dmitry I. Gabrilovich, Lucia R. Languino, Andrew R. Cohen & Dario C. Altieri
Nature Communications7, Article number: 13730 (2016)
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