Autophagy Suppresses Tumorigenesis Through Elimination of p62

By Robin Mathew, Cristina M. Karp, Brian Beaudoin, N. Vuong, Guanghua Chen, Hsin-Yi Chen, Kevin Bray, Anupama Reddy, G. Bhanot, C. Gélinas and 3 more. Cell, 2009

1,056 citations recorded by the source corpus.

SUMMARY Allelic loss of the essential autophagy gene beclin1 occurs in human cancers and renders mice tumor-prone suggesting that autophagy is a tumor-suppression mechanism. While tumor cells utilize autophagy to survive metabolic stress, autophagy also mitigates the resulting cellular damage that may limit tumorigenesis. In response to stress, autophagy-defective tumor cells preferentially accumulate p62/SQSTM1 (p62), endoplasmic reticulum (ER) chaperones, damaged mitochondria, reactive oxygen species (ROS), and genome damage. Moreover, suppressing ROS or p62 accumulation prevented damage resulting from autophagy defects indicating that failure to regulate p62 caused oxidative stress. Importantly, sustained p62 expression resulting from autophagy defects was sufficient to alter NF-κB regulation and gene expression and to promote tumorigenesis. Thus defective autophagy is a mechanism for p62 upregulation commonly observed in human tumors that contributes directly to tumorigenesis likely by perturbing the signal transduction adaptor function of p62 controlling pathways critical for oncogenesis.

Subfields: Cell Biology, Epidemiology, Oncology

View Paper: https://www.semanticscholar.org/paper/3eee3e8b154e1eb3a25b2906eca3d4a5511e2d4e

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Citations in the corpus

Autophagy-deficient mice develop multiple liver tumors. (2011, methodology): “…far proposed in cell culture and allografted tumor models include suppression of tumorigenic inflammation (Degenhardt et al. 2006), mitigation of metabolic stress and genomic damage (KarantzaWadsworth et al. 2007; Mathew et al. 2007), and p62 (also called SQSTM1) degradation (Mathew et al. 2009).”
Autophagy in malignant transformation and cancer progression (2015, positive): “…functions, including a key role in the transduction of RAS-elicited signals as well as in the activation of a feedforward loop involving the cyto-protective transcription factor NF-j B driven by oncogenic stress (Duran et al , 2008; Mathew et al , 2009; Takamura et al , 2011; Ling et al , 2012).”
Autophagy and autophagy-related proteins in cancer (2020, background): “Autophagy functioning as a cancer promotion mechanism is mainly based on its role involved in removing damaged mitochondria, inhibiting DNA damage, maintaining genome stability, limiting inflammation, and finally preventing cancer cell damage under the conditions of stress [14, 213, 232].”
Autophagy-Independent Functions of the Autophagy Machinery (2019, background): “, 2012), even though bona fide autophagic responses are known to contribute to themaintenance of genomic homeostasis (Karantza-Wadsworth et al., 2007; Mathew et al., 2009).”
Autophagy, Metabolism, and Cancer (2015, positive): “Gain of p62 also promotes tumorigenesis (14) and the growth of FAK family-interacting protein 386 of 200 kDa (FIP200)-deficient tumors (32).”
Erratum: Autophagy suppresses tumorigenesis through elimination of p62 (Cell (2009) 137 (1062-1075)) (2011, neutral): “Mathew and colleagues reported that autophagy suppresses tumorigenesis through elimination of p62[4].”