Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance and recurrence disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy. Molecular evidences suggest that deregulation of mitochondrial biogenesis, morphology, dynamics and apoptosis is involved in carcinogenesis. However, these mitochondrial processes remain to be investigated in OC. Eighteen controls and sixteen OC tissues (serous and mucinous) were collected. Enzymatic activities were performed spectrophotometrically, mtDNA content was measured by real-time-PCR, protein levels by western blotting, mitochondrial number and structure by electron microscopy. Statistical analysis were performed by Student' t-test, Mann-Whitney’s and principal component analysis (PCA). We found, in OC, increased mitochondrial number associated with increased PGC1α, TFAM protein levels and mtDNA content. The OC mitochondria presented an increased maximum length, reduced cristae width and junction diameter associated with increased OPA1 and PHB2 protein levels. In addition, in OC tissues, augmented cAMP and SIRT3 protein levels were observed. PCA of twenty-five biochemical parameters analyzed, classified OC patients in a distinct group from controls. We highlight a “mitochondrial signature” in OC that could result from cooperation of cAMP pathway, SIRT3, OPA1 and PHB2 proteins.
|Titolo:||Human ovarian cancer tissue exhibits increase of mitochondrial biogenesis and cristae remodeling|
SIGNORILE, ANNA (Corresponding)
|Data di pubblicazione:||2019|
|Appare nelle tipologie:||1.1 Articolo in rivista|