High Expression of the Mitophagy-Related Protein Pink1 is Associated with a Poor Response to Chemotherapy and a Poor Prognosis for Patients Treated with Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

Yamashita, Kotaro; Miyata, Hiroshi; Makino, Tomoki; Masuike, Yasunori; Furukawa, H; Tanaka, Koji; Miyazaki, Yasuhiro; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Nakajima, Kiyokazu; Takiguchi, Shuji; Morii, Eiichi; Mori, Masaki; Doki, Yuichiro

doi:10.1245/s10434-017-6096-8

Cited by 48 publications

(48 citation statements)

References 31 publications

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“…Notably, we newly identified PINK1 as a protective prognostic factor in ESCA (esophageal adenocarcinoma) (OS: log rank P = 0.039) ( Figure 3B). This discovery might challenge a previous report stating that high expression of PINK1 is a poor prognostic factor for patients with esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy (35). For HNSC (head and neck squamous cell carcinoma), PINK1 was identified as a protective prognostic factor (OS: log rank P = 0.0072) ( Figure 3C).…”

Section: Prognostic Value Of Pink1 Across Cancersmentioning

confidence: 62%

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Zhu

Jiang

et al. 2020

Front. Oncol.

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Section: Prognostic Value Of Pink1 Across Cancersmentioning

confidence: 62%

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Zhu

Jiang

et al. 2020

Front. Oncol.

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“…PINK1 (PARK6) a kinase involved in the regulation of autophagy and the cell cycle, has been involved in glioblastoma, and ovarian cancers (Berthier et al, 2011 ; Devine et al, 2011 ; O’Flanagan et al, 2016 ). Recently, PINK1 expression has been associated with poor response to chemotherapy (Yamashita et al, 2017 ). Mutations in DJ1 (PARK7, a regulator of the tumor suppressor PTEN) is observed in PD patients and in breast, lung, pancreatic, gastric and prostate cancers (Hod, 2004 ; He et al, 2011 ; Zeng et al, 2011 ; Kawate et al, 2013 ; Li et al, 2013 ).…”

Section: Cancer and Parkinson’s Diseasementioning

confidence: 99%

Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

Santiago

Bottero

Potashkin

2017

Front. Aging Neurosci.

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A wide spectrum of comorbidities has been associated with Parkinson’s disease (PD), a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms. Further, drugs to treat diabetes and cancer have elicited neuroprotective effects in PD models. Nonetheless, the mechanisms underlying the occurrence of these comorbidities remain elusive. Herein, we discuss the biological and clinical implications of comorbidities in the pathogenesis, progression, and clinical management, with an emphasis on personalized medicine applications for PD.

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“…Increased mitochondrial turnover would depend on increased fission and mitophagy to eliminate damaged mitochondria, together with increased mitochondrial biogenesis and fusion to repopulate cells with fit mitochondria. Interestingly, a high mitophagic rate has been reported to be associated with chemoresistance in several cancer cell types (Su et al, 2016;Villa et al, 2017;Yamashita et al, 2017;Naik et al, 2018), and Zheng et al (2015) further observed that mitophagy participates in hypoxia-induced radioresistance in breast cancer cell lines. There is also good evidence that a high rate of mitochondrial biogenesis, primarily depending on activation of mitochondrial transcription factor A (TFAM) and transcription coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), participates in chemoresistance (Gabrielson et al, 2014;Wu et al, 2016;Shen et al, 2018;Hu and Guo, 2019).…”

Section: Discussionmentioning

confidence: 90%

Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells

et al. 2020

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The clinical management of head and neck squamous cell carcinoma (HNSCC) commonly involves chemoradiotherapy, but recurrences often occur that are associated with radioresistance. Using human SQD9 laryngeal squamous cell carcinoma cancer cells as a model, we aimed to identify metabolic changes associated with acquired radioresistance. In a top-down approach, matched radiosensitive and radioresistant SQD9 cells were generated and metabolically compared, focusing on glycolysis, oxidative phosphorylation (OXPHOS) and ROS production. The cell cycle, clonogenicity, tumor growth in mice and DNA damage-repair were assessed. Mitochondrial DNA (mtDNA) was sequenced. In a bottom-up approach, matched glycolytic and oxidative SQD9 cells were generated using FACS-sorting, and tested for their radiosensitivity/radioresistance. We found that acquired radioresistance is associated with a shift from a glycolytic to a more oxidative metabolism in SQD9 cells. The opposite was also true, as the most oxidative fraction isolated from SQD9 wild-type cells was also more radioresistant than the most glycolytic fraction. However, neither reduced hexokinase expression nor OXPHOS were directly responsible for the radioresistant phenotype. Radiosensitive and radioresistant cells had similar proliferation rates and were equally efficient for ATP production. They were equally sensitive to redox stress and had similar DNA damage repair, but radioresistant cells had an increased number of mitochondria and a higher mtDNA content. Thus, an oxidative switch is associated with but is not responsible for acquired radioresistance in human SQD9 cells. In radioresistant cells, more abundant and fitter mitochondria could help to preserve mitochondrial functions upon irradiation.

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High Expression of the Mitophagy-Related Protein Pink1 is Associated with a Poor Response to Chemotherapy and a Poor Prognosis for Patients Treated with Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

Abstract: High expression of Pink1 is associated with chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant chemotherapy.

Cited by 48 publications

References 31 publications

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells

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