Quantitative analysis of the human ovarian carcinoma mitochondrial phosphoproteome

Abstract

To investigate the existence and their potential biological roles of mitochondrial phosphoproteins (mtPPs) in human ovarian carcinoma (OC), mitochondria purified from OC and control tissues were analyzed with TiO2 enrichment-based iTRAQ quantitative proteomics. Totally 67 mtPPs with 124 phosphorylation sites were identified, which of them included 48 differential mtPPs (mtDPPs). Eighteen mtPPs were reported previously in OCs, and they were consistent in this study compared to previous literature. GO analysis revealed those mtPPs were involved in multiple cellular processes. PPI network indicated that those mtPPs were correlated mutually, and some mtPPs acted as hub molecules, such as EIF2S2, RPLP0, RPLP2, CFL1, MYH10, HSP90, HSPD1, PSMA3, TMX1, VDAC2, VDAC3, TOMM22, and TOMM20. Totally 32 mtPP-pathway systems (p<0.05) were enriched and clustered into 15 groups, including mitophagy, apoptosis, deubiquitination, signaling by VEGF, RHO-GTPase effectors, mitochondrial protein import, translation initiation, RNA transport, cellular responses to stress, and c-MYC transcriptional activation. Totally 29 mtPPs contained a certain protein domains. Upstream regulation analysis showed that TP53, TGFB1, dexamethasone, and thapsigargin might act as inhibitors, and L-dopa and forskolin might act as activators. This study provided novel insights into mitochondrial protein phosphorylations and their potential roles in OC pathogenesis and offered new biomarker resource for OCs.

Functional genomic analysis identifies drug targetable pathways in invasive and metastatic cutaneous squamous cell carcinoma

“…Other well-characterized oncogenes also present in the EPHA-ephrin signaling pathway include TIAM, YES1, and HRAS (Yang et al 2015;Dotto and Rustgi 2016;Garmendia et al 2019). MYH10, the only pathway member in our cohort with alterations in both single-nucleotide variation (SNV) and copy-number variation (CNV), has been identified as an important hub in other quantitative analyses and plays an important role in cancer migration and invasion (Wang et al 2018;Guo et al 2019;Li et al 2019). These data combined with our HitWalker2 analyses suggest great therapeutic potential in targeting RAC1 and other members of the Eph-ephrin pathway in cSCC.…”

The Mitochondrial Proteome of Tumor Cells: A SnapShot on Methodological Approaches and New Biomarkers

“…These techniques have been recently used to analyze the mitochondrial proteome of cancer tissues. For example, Li N. et al used iTRAQ quantitative proteomic to analyze the mitochondrial proteome and phospho-proteome of ovarian cancers and control ovarian tissues [ 76 , 77 ]. In the first screening, they identified approximately 5000 proteins from purified mitochondrial samples: 262 of them were associated with overall survival of ovarian cancer patients and 63 were identified as potential ovarian cancer biomarkers [ 76 ].…”

“…In a follow-up paper, using an iTRAQ-TiO 2 enrichment-LC-MS/MS experimental approach the authors identified 67 mitochondrial proteins that were phosphorylated in control and ovarian cancer samples. Among them, 48 proteins were differentially phosphorylated in cancer compared to controls [ 77 ].…”

<p>The Novel Zinc Finger Protein 587B Gene, ZNF587B, Regulates Cell Proliferation and Metastasis in Ovarian Cancer Cells in vivo and in vitro</p>

“…Tumor volumes were calculated as 0.5 LW. 2 Mice were sacrificed by intraperitoneal injection with 200 μL of 10% chloral hydrate when the tumor volume was 200-300 mm 3 . Tumors were excised after the skin was disinfected, placed in approximately 1.5 mm 3 normal saline, inoculated into the animal's bilateral armpit with a trocar, and the skin wound was disinfected with iodophor.…”

“…1 More than 70% of patients are diagnosed at an advanced stage III or IV (International Federation of Gynecology and Obstetrics, FIGO) with distant metastases. [2][3][4] The standard therapy for OC is platinum-based chemotherapy following cytoreductive surgery. 5 Generally, most patients have a high initial response rate to cisplatin.…”