2021
DOI: 10.1111/cas.15125
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PDK2 leads to cisplatin resistance through suppression of mitochondrial function in ovarian clear cell carcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Cited by 21 publications
(19 citation statements)
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“…Notably, we detected correlation of PDK2 high expression with higher biochemical recurrence and lower disease-free survival, suggesting a pro-oncogenic role for PDK2 in PCa. This is in line with the proposed oncogenicity of PDK2 overexpression in other cancer types ( 50 , 51 ). The tumor suppressor p53 negatively regulates PDK2 transcription ( 52 ), making of interest the analysis of the participation of p53 in the regulation of PDK2 expression in PCa cells.…”
Section: Discussionsupporting
confidence: 90%
“…Notably, we detected correlation of PDK2 high expression with higher biochemical recurrence and lower disease-free survival, suggesting a pro-oncogenic role for PDK2 in PCa. This is in line with the proposed oncogenicity of PDK2 overexpression in other cancer types ( 50 , 51 ). The tumor suppressor p53 negatively regulates PDK2 transcription ( 52 ), making of interest the analysis of the participation of p53 in the regulation of PDK2 expression in PCa cells.…”
Section: Discussionsupporting
confidence: 90%
“…High expression of PDK1 has been correlated to tumor size, the International Federation of Gynecology and Obstetrics (FIGO) stage, metastases, and overall survival [ 26 ]. Moreover, PDK2 [ 27 ] and PDK4 [ 28 ] have been reported to promote cisplatin resistance in ovarian CCC by suppressing mitochondrial OXPHOS. Additionally, their high levels are associated with a poor prognosis in patients with ovarian cancer.…”
Section: Resultsmentioning
confidence: 99%
“…DCA : Dichloroacetic acid (DCA) reversed the Warburg effect by inhibiting the PDK1-induced metabolic switch from mitochondrial OXPHOS toward glycolysis [ 9 , 11 , 24 , 83 , 84 ]. Furthermore, inhibition of PDKs (e.g., dicumarol, a coumarin compound) reversed cisplatin resistance by increasing the production of mitochondrial ROS [ 9 , 27 ].…”
Section: Resultsmentioning
confidence: 99%
“…In ovarian cancer cells, abnormal elevation of PDK1 can upregulate programmed death ligand-1 (PD-L1) expression and induce increased apoptosis of CD8 + T cells, ultimately impairing T cell immune function (80). Pyruvate dehydrogenase kinase 2 (PDK2) is favorably connected with the prognosis of OCCC, and increased PDK2 expression decreases apoptosis, resulting in cisplatin resistance in OCCC (81). By increasing the production of reactive oxygen species although mitochondrial metabolism, PDK2 inhibition can synergistically boost sensitivity to cisplatin (81).…”
Section: Glucose Metabolismmentioning
confidence: 99%
“…Pyruvate dehydrogenase kinase 2 (PDK2) is favorably connected with the prognosis of OCCC, and increased PDK2 expression decreases apoptosis, resulting in cisplatin resistance in OCCC (81). By increasing the production of reactive oxygen species although mitochondrial metabolism, PDK2 inhibition can synergistically boost sensitivity to cisplatin (81). Another classical metabolic reprogramming occurs in the TCA cycle of macrophages.…”
Section: Glucose Metabolismmentioning
confidence: 99%