Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer

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dc.contributor.authorGrieco, Joseph P.en
dc.contributor.authorAllen, Mitchell E.en
dc.contributor.authorPerry, Justin B.en
dc.contributor.authorWang, Yaoen
dc.contributor.authorSong, Yipeien
dc.contributor.authorRohani, Alien
dc.contributor.authorCompton, Stephanie L. E.en
dc.contributor.authorSmyth, James W.en
dc.contributor.authorSwami, Nathan S.en
dc.contributor.authorBrown, David A.en
dc.contributor.authorSchmelz, Eva M.en
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.date.accessioned2021-06-02T12:55:20Zen
dc.date.available2021-06-02T12:55:20Zen
dc.date.issued2021-01-13en
dc.description.abstractOvarian cancer is the deadliest gynecological cancer in women, with a survival rate of less than 30% when the cancer has spread throughout the peritoneal cavity. Aggregation of cancer cells increases their viability and metastatic potential; however, there are limited studies that correlate these functional changes to specific phenotypic alterations. In this study, we investigated changes in mitochondrial morphology and dynamics during malignant transition using our MOSE cell model for progressive serous ovarian cancer. Mitochondrial morphology was changed with increasing malignancy from a filamentous network to single, enlarged organelles due to an imbalance of mitochondrial dynamic proteins (fusion: MFN1/OPA1, fission: DRP1/FIS1). These phenotypic alterations aided the adaptation to hypoxia through the promotion of autophagy and were accompanied by changes in the mitochondrial ultrastructure, mitochondrial membrane potential, and the regulation of reactive oxygen species (ROS) levels. The tumor-initiating cells increased mitochondrial fragmentation after aggregation and exposure to hypoxia that correlated well with our previously observed reduced growth and respiration in spheroids, suggesting that these alterations promote viability in non-permissive conditions. Our identification of such mitochondrial phenotypic changes in malignancy provides a model in which to identify targets for interventions aimed at suppressing metastases.en
dc.description.notesThis work is supported by the USDA National Institute of Food and Agriculture Hatch project 1006578 (ES), CEH seed funds (ES), NIH NHLBI R01 grant HL132236 (JS), NIH Grant R01 CA200755 (NS), UVA Cancer Center Seeds Funds (NS). NS was supported in part by the National Institutes of Health's National Center for Advancing Translational Sciences under Award number UL1TR003015 and R01 CA200755. This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.en
dc.description.sponsorshipUSDA National Institute of Food and Agriculture Hatch project [1006578]; CEH seed funds; NIH NHLBI R01 grant [HL132236]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 CA200755]; UVA Cancer Center Seeds Funds; National Institutes of Health's National Center for Advancing Translational Sciences [R01 CA200755, UL1TR003015]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fonc.2020.600113en
dc.identifier.issn2234-943Xen
dc.identifier.other600113en
dc.identifier.pmid33520711en
dc.identifier.urihttp://hdl.handle.net/10919/103564en
dc.identifier.volume10en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectspheroidsen
dc.subjecthypoxiaen
dc.subjectfragmentationen
dc.subjectfusionen
dc.subjectfissionen
dc.subjectuncoupling proteinen
dc.subjectreactive oxygen speciesen
dc.subjectmitophagyen
dc.titleProgression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Canceren
dc.title.serialFrontiers in Oncologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Scholarly Works, Human Nutrition, Foods, and Exercise
Scholarly Works, Biological Sciences
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