PINK1 signalling in cancer biology

O’Flanagan, Ciara H.; O’Neill, Cora

doi:10.1016/j.bbcan.2014.10.006

Cited by 42 publications

(47 citation statements)

References 167 publications

(277 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PINK1 has important pro-survival, anti-apoptotic, and cytoprotective functions, suggesting that it may be a promising target for cancer therapies [15]. PINK1 deletion reduces, and PINK1 overexpression restores, cancer cell proliferation, colony formation, and invasiveness, indicating that PINK1 promotes cell cycle progression and acts as an oncogene [45].…”

Section: Discussionmentioning

confidence: 99%

“…PINK1 also regulates apoptosis and cell growth in breast cancer cells [14]. Because PINK1 regulates cancer cell survival, stress resistance, mitochondrial homeostasis, and cell cycle progression, it may serve as a therapeutic target or a predictive biomarker of response to treatment in cancer patients [15]. Inhibition of the fusion–fission cycle using the DRP1 inhibitor mdivi-1 prevents mitophagy, demonstrating the importance of mitochondrial fission in mitophagy [16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Shen

et al. 2017

Oncotarget

View full text Add to dashboard Cite

The molecular mechanisms underlying the anti-breast cancer effects of polyphyllin I, a natural compound extracted from Paris polyphylla rhizomes, are not fully understood. In the present study, we found that polyphyllin I induces mitochondrial translocation of DRP1 by dephosphorylating DRP1 at Ser637, leading to mitochondrial fission, cytochrome c release from mitochondria into the cytosol and, ultimately apoptosis. Polyphyllin I also increased the stabilization of full-length PINK1 at the mitochondrial surface, leading to the recruitment of PARK2, P62, ubiquitin, and LC3B-II to mitochondria and culminating in mitophagy. PINK1 knockdown markedly suppressed polyphyllin I-induced mitophagy and enhanced polyphyllin I-induced, DRP1-dependent mitochondrial fission and apoptosis. Furthermore, suppression of DRP1 by mdivi-1 or shRNA inhibited PINK1 knockdown/polyphyllin I-induced mitochondrial fragmentation and apoptosis, suggesting that PINK1 depletion leads to excessive fission and, subsequently, mitochondrial fragmentation. An in vivo study confirmed that polyphyllin I greatly inhibited tumor growth and induced apoptosis in MDA-MB-231 xenografts, and these effects were enhanced by PINK1 knockdown. These data describe the mechanism by which PINK1 contributes to polyphyllin I-induced mitophagy and apoptosis and suggest that polyphyllin I may be an effective drug for breast cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Shen

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Overexpression and aggregation of α-synuclein exacerbate impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells (Parihar et al, 2009); α-synuclein is related to the pathology (Roberts et al, 2015) and cardiovascular dysautonomia (Jain & Goldstein, 2012) of PD. Likewise, PTEN/ PI3K/Akt and Pink/Parkin are associated with cancer (O'Flanagan & O'Neill, 2014;Zhang et al, 2015), PD (Haque et al, 2008) and cardiovascular disease (Takeuchi & Sata, 2012).…”

Section: Activation Of Endogenous Dj-1 As a Common Therapeutic Targetmentioning

confidence: 99%

Activation of endogenous antioxidants as a common therapeutic strategy against cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1

Chan

2015

Pharmacology & Therapeutics

View full text Add to dashboard Cite

“…So far, the functional role of ATG5 in breast cancer is unknown. On the other hand, PTEN is a well-defined TSG and the regulator of PINK1 (19). CDH1 is a key molecule of the cell-cell adhesion complex, and its loss promotes metastasis (20,21).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Reprogramming Regulates Breast Cancer Progression

Kannan

Wells

Sivakumar³

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The goal of this study was to understand the role of altered mitochondrial function in breast cancer progression and determine the potential of the molecular alteration signature in developing exosome-based biomarkers.Experimental Design: This study was designed to characterize the critical components regulating mitochondrial function in breast tumorigenesis. Experiments were conducted to assess the potential of these molecules for exosome-based biomarker development.Results: We observed a remarkable reduction in spontaneous metastases through the interplay in mitochondria by SH3GL2, vesicular endocytosis-associated protein and MFN2, an important regulator of mitochondrial fusion. Following its overexpression in breast cancer cells, SH3GL2 translocated to mitochondria and induced the production of superoxide and release of cytochrome C from mitochondria to the cytoplasm. These molecular changes were accompanied by decreased lung and liver metastases and primary tumor growth. SH3GL2 depletion reversed the above phenotypic and associated molecular changes in nontumorigenic and tumorigenic breast epithelial cells. Loss of SH3GL2 and MFN2 expression was evident in primary human breast cancer tissues and their positive lymph nodes, which was associated with disease progression. SH3GL2 and MFN2 expression was detected in sera exosomes of normal healthy women, but barely detectable in the majority of the women with breast cancer exhibiting SH3GL2 and MFN2 loss in their primary tumors.Conclusions: This study identified a new mitochondria reprogramming pathway influencing breast cancer progression through SH3GL2 and MFN2. These proteins were frequently lost in breast cancer, which was traceable in the circulating exosomes. Clin Cancer Res; 22(13); 3348-60. Ó2016 AACR.

show abstract

PINK1 signalling in cancer biology

Cited by 42 publications

References 167 publications

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Activation of endogenous antioxidants as a common therapeutic strategy against cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1

Mitochondrial Reprogramming Regulates Breast Cancer Progression

Contact Info

Product

Resources

About