Parkin protein expression and its impact on survival of patients with advanced colorectal cancer

Silva-Camargo, Claudia Caroline Veloso da; Baldin, Rosimeri Kühl Svoboda; Polli, Nayanne Louise Costacurta; Agostinho, Amanda Pereira; Olandosk, Marcia; Noronha, Lúcia de; Sotomaior, Vanessa Santos

doi:10.20892/j.issn.2095-3941.2017.0136

Cited by 19 publications

(7 citation statements)

References 45 publications

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“…Interestingly, some colorectal cancer cell lines contain mutated forms of PRKN and may use alternate mechanisms to activate mitophagy [38]. Research is starting to investigate how PRKN may be used as a prognostic marker in CRC as it may correlate with invasion and overall survival [39].…”

Section: Autophagy Subtypesmentioning

confidence: 99%

Functions and Implications of Autophagy in Colon Cancer

Devenport

Shah

2019

Cells

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Autophagy is an essential function to breakdown cellular proteins and organelles to recycle for new nutrient building blocks. In colorectal cancer, the importance of autophagy is becoming widely recognized as it demonstrates both pro- and anti-tumorigenic functions. In colon cancer, cell autonomous and non-autonomous roles for autophagy are essential in growth and progression. However, the mechanisms downstream of autophagy (to reduce or enhance tumor growth) are not well known. Additionally, the signals that activate and coordinate autophagy for tumor cell growth and survival are not clear. Here, we highlight the context- and cargo-dependent role of autophagy in proliferation, cell death, and cargo breakdown.

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Section: Autophagy Subtypesmentioning

confidence: 99%

Functions and Implications of Autophagy in Colon Cancer

Devenport

Shah

2019

Cells

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“…Although the precise association between PARK2 and cancer susceptibility is not well-understood, the deletion, copy number alteration, mutations, and protein expression of PARK2 have been found in several types of cancers, such as glioblastoma, breast, ovarian, liver, colorectal, and lung (15, 17–25). Xiong et al have identified PARK2 mutation as a single genetic susceptibility factor for lung cancer (19) and it could become an independent prognostic marker in advanced colorectal cancer (26). Inactivation of PARK2 may play a critical role in carcinogenesis (27).…”

Section: Introductionmentioning

confidence: 99%

PARK2 Suppresses Proliferation and Tumorigenicity in Non-small Cell Lung Cancer

Duan

Zhong

et al. 2019

Front. Oncol.

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Aims: PARK2 mutation is originally associated with the progression of Parkinson's disease. In recent years, PARK2 has been reported as a tumor suppressor gene in various cancers, including lung cancer. However, the biological functions and potential molecular mechanisms of PARK2 in non-small cell lung cancer (NSCLC) are still unclear. Methods: The level of PARK2 expression in 32 tissue samples of NSCLC and matched non-tumor lung tissues was detected by Western blot, and 64 specimens of NSCLC tissues were detected by immunohistochemistry. H1299 and H460 cell lines were used to PARK2 overexpression models, and H460 cell line was also used to PARK2 knockdown model. Using cell viability, colony formation, cell cycle, apoptosis, migration, and invasion assay, the biological functions of PARK2 were evaluated and the potential molecular mechanism of PARK2 was investigated in vitro . Meanwhile, 22 nude mice were employed for in vivo studies. Results: Western blot analysis revealed a decrease of PARK2 protein expression in human NSCLC samples. Immunohistochemistry also identified a vastly reduced expression of PARK2 in NSCLC (72%) and low PARK2 expression was significantly associated with tumor histological grade, lymph node metastasis and advanced TNM stage. Overexpression of PARK2 suppressed cell proliferation, colony formation, migration, and invasion, arrested cell cycle progression in the G1 phase, and induced apoptosis in human non-small cell lines H1299 and H460 in vitro . Meanwhile, knockdown of PARK2 had the opposite biological functions. In addition, PARK2 significantly decreased the tumor volumes in subcutaneous xenograft model and reduced the incidence of metastatic tumors in the transfer model. Exploration of the molecular mechanism of PARK2 in NSCLC showed that PARK2 negatively regulated the EGFR/AKT/mTOR signaling pathway. Conclusions: PARK2 was an important tumor suppressor in NSCLC, which might inhibit cancer growth and metastases through the down regulation of the EGFR/AKT/mTOR signaling pathway.

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“…Clinically, the expression of PRKN is prognostic in patient outcome. Decreased PRNK expression is correlated with increased survival ( 57 ); however, increased expression is found with enhanced invasion in tumors ( 57 ). Our work highlights that the dual nature of autophagy and mitophagy in cancer growth could be attributed to available nutrient status.…”

Section: Discussionmentioning

confidence: 99%

Colorectal cancer cells utilize autophagy to maintain mitochondrial metabolism for cell proliferation under nutrient stress

Devenport¹,

Singhal²,

Radyk³

et al. 2021

JCI Insight

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Cancer cells re-program cellular metabolism to maintain adequate nutrient pools to sustain proliferation. Moreover, autophagy is a regulated mechanism to breakdown dysfunctional cellular components and recycle cellular nutrients. However, the requirement for autophagy and the integration in cancer cell metabolism is not clear in colon cancer. Here we show a cell-autonomous dependency of autophagy for cell growth in colorectal cancer. Loss of epithelial autophagy inhibits tumor growth in both sporadic and colitis associated cancer models.Genetic and pharmacological inhibition of autophagy inhibits cell growth in colon cancerderived cell lines and patient-derived enteroid models. Importantly, normal colon epithelium and patient-derived normal enteroid growth was not decreased following autophagy inhibition. To couple the role of autophagy to cellular metabolism, a cell culture screen in conjunction with metabolomic analysis was performed. We identified a critical role of autophagy to maintain mitochondrial metabolites for growth. Loss of mitochondrial recycling through inhibition of mitophagy hinders colon cancer cell growth. These findings have revealed a cell-autonomous role of autophagy that plays a critical role in regulating nutrient pools in vivo and in cell models and provides therapeutic targets for colon cancer.

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Parkin protein expression and its impact on survival of patients with advanced colorectal cancer

Cited by 19 publications

References 45 publications

Functions and Implications of Autophagy in Colon Cancer

Functions and Implications of Autophagy in Colon Cancer

PARK2 Suppresses Proliferation and Tumorigenicity in Non-small Cell Lung Cancer

Colorectal cancer cells utilize autophagy to maintain mitochondrial metabolism for cell proliferation under nutrient stress

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