p62 promotes proliferation, apoptosis‑resistance and invasion of prostate cancer cells through the Keap1/Nrf2/ARE axis

Jiang, Ganggang; Li, Xue; Huang, Yiqiao; Lan, Ziquan; Zhang, Zhiming; Su, Zhengming; Fang, Zhiyuan; Lai, Yuxiong; Yao, Wenqian; Liu, Ting; Hu, La; Wang, Fen; Huang, Hai; Liu, Leyuan

doi:10.3892/or.2020.7527

Cited by 19 publications

(27 citation statements)

References 41 publications

(47 reference statements)

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“…In addition, immunohistochemistry analysis of tumors derived from patients with non-small cell lung cancer demonstrated an association between high expression of p62 and the aggressiveness of the tumor ( 70 ). A similar correlation was also reported in patients with colorectal cancer, osteosarcoma, prostate cancer, hepatocellular carcinoma, breast cancer, and acute myeloid leukemia, among others ( 71 – 75 ).…”

Section: Molecular Features Of Autophagy Cytosolic Receptorssupporting

confidence: 83%

“…Finally, same findings have been reported in the cellular model of prostate cancer DU145, characterized by high levels of p62. Indeed, silencing of p62 in DU145 cells decrease cell proliferation, apoptosis-resistance and invasion by a mechanism related with the inactivation of the NRF2 pathway ( 75 , 89 ). Altogether, these findings demonstrate the role of the axis p62/NRF2 in tumor progression in different types of cancer.…”

Section: Molecular Features Of Autophagy Cytosolic Receptorsmentioning

confidence: 99%

“…Among all autophagy receptors identified, p62 is by far the most characterized one, currently considered a good predictor marker of the grade of malignancy in several types of cancer ( 71 – 75 ). Since the pro-tumoral effects of p62 are not only related with the degradation of specific cargos such as what occurs with VDR or damaged mitochondria, it opens the possibility of non-canonical roles of p62 mostly related with the stability of certain proteins like NRF2, TWIST1 and Vimentin ( 65 , 71 , 75 , 80 , 87 ). A challenge for the future to better understand the contribution of p62 during cancer progression is the identification of novel cargos of this receptor, considering specific types of cancer cells including cancer stem cells.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Pro-Tumoral Functions of Autophagy Receptors in the Modulation of Cancer Progression

2021

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Cancer progression involves a variety of pro-tumorigenic biological processes including cell proliferation, migration, invasion, and survival. A cellular pathway implicated in these pro-tumorigenic processes is autophagy, a catabolic route used for recycling of cytoplasmic components to generate macromolecular building blocks and energy, under stress conditions, to remove damaged cellular constituents to adapt to changing nutrient conditions and to maintain cellular homeostasis. During autophagy, cells form a double-membrane sequestering a compartment termed the phagophore, which matures into an autophagosome. Following fusion with the lysosome, the cargo is degraded inside the autolysosomes and the resulting macromolecules released back into the cytosol for reuse. Cancer cells use this recycling system during cancer progression, however the key autophagy players involved in this disease is unclear. Accumulative evidences show that autophagy receptors, crucial players for selective autophagy, are overexpressed during cancer progression, yet the mechanisms whereby pro-tumorigenic biological processes are modulated by these receptors remains unknown. In this review, we summarized the most important findings related with the pro-tumorigenic role of autophagy receptors p62/SQSTM1, NBR1, NDP52, and OPTN in cancer progression. In addition, we showed the most relevant cargos degraded by these receptors that have been shown to function as critical regulators of pro-tumorigenic processes. Finally, we discussed the role of autophagy receptors in the context of the cellular pathways implicated in this disease, such as growth factors signaling, oxidative stress response and apoptosis. In summary, we highlight that autophagy receptors should be considered important players of cancer progression, which could offer a niche for the development of novel diagnosis and cancer treatment strategies.

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Section: Molecular Features Of Autophagy Cytosolic Receptorssupporting

confidence: 83%

Section: Molecular Features Of Autophagy Cytosolic Receptorsmentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Pro-Tumoral Functions of Autophagy Receptors in the Modulation of Cancer Progression

2021

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“…It seems that Nrf2 can enhance tumor-initiating cell lineage that subsequently, mediates chemoresistance [79]. The p53 can provide proteasomal degradation of Keap1 via inducing Nrf2/ARE signaling to promote proliferation and apoptosis inhibition, resulting in chemoresistance [80]. Upon Nrf2 activation, glutamine metabolism increases to induce chemoresistance, and is associated with poor prognosis of cancer patients [81].…”

Section: Nrf2 In Protection and Chemoresistancementioning

confidence: 99%

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

et al. 2021

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Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dose-dependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review.

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“…In contrast, autophagy is a self-defense mechanism by which PCa cells withstand excessive oxidative stress. Especially when there exists a high level of p62 in PCa cells, autophagy can cause the degradation of Keap1 depending on the direct physical interaction between Keap1 and p62, thus limiting ROS amplification through Nrf2/ARE axis [ 182 , 183 ].…”

Section: Roles Of Ros Molecules In Pcamentioning

confidence: 99%

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

Han

Wang

et al. 2020

BioMed Research International

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Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.

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p62 promotes proliferation, apoptosis‑resistance and invasion of prostate cancer cells through the Keap1/Nrf2/ARE axis

Cited by 19 publications

References 41 publications

Pro-Tumoral Functions of Autophagy Receptors in the Modulation of Cancer Progression

Pro-Tumoral Functions of Autophagy Receptors in the Modulation of Cancer Progression

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

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