Autophagic Regulation of p62 is Critical for Cancer Therapy

Islam, Md Ariful; Sooro, Mopa Alina; Zhang, Pinghu

doi:10.3390/ijms19051405

Cited by 189 publications

(145 citation statements)

References 100 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…The level of LC3 per se indicates that autophagy is initiated, but may not reflect upon whether autophagy has proceeded or become impaired [21,31]. A proceeding autophagy implies a low level of p62 since this protein becomes degraded together with the cargo in the autophago-lysosome [32]. Thus, increased LC3 and p62 in AIH suggest that autophagosome formation has occurred without an increase in lysosomal degradation, as has been demonstrated in case of p62 in a recent study [33].…”

Section: Discussionmentioning

confidence: 89%

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

Szekerczés

Gógl

Illyés

et al. 2020

Pathol. Oncol. Res.

View full text Add to dashboard Cite

Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and − 224) known to be involved in the regulation of autophagy. In addition, the expression levels were related to pathohistological parameters. Liver biopsy samples, including 45 CHC and 18 AIH cases, were immunohistochemically stained for LC3, p62 and TOMM20 and the expression of miRNAs was determined using real-time PCR. We found elevated LC3 and p62 in AIH samples as compared with CHC ones, indicating an activated autophagy that is impaired in AIH as no degradation of p62 seemed to occur. Moreover, p62 showed strong correlation with necroinflammatory grades in the AIH group. The observed elevated levels of TOMM20 and p62 suggest a less efficient elimination of damaged mitochondria in AIH as opposed to CHC, in which autophagy seems to have a more active function. The level of miR-101 was increased in case of CHC as compared with AIH, however, miR-155, -204 and 224 resulted in no expressional. Furthermore, miR-224 level correlated with steatosis and miR-155 expression with fibrosis stage in CHC. In conclusion, dissimilar autophagic activity was observed in CHC and AIH, suggesting a close association between impaired autophagy and severity of necroinflammation. This impairment may not be regulated by the analyzed miRNAs. Nevertheless, miR-224 and − 155 seem to be associated with CHC progression.

show abstract

Section: Discussionmentioning

confidence: 89%

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

Szekerczés

Gógl

Illyés

et al. 2020

Pathol. Oncol. Res.

View full text Add to dashboard Cite

show abstract

“…The results indicated that curcumin induces apoptosis by regulating PARP, c‐PARP, caspase‐9, and caspase‐3 expression, whereas THC induces autophagy by regulating p62 and LC3 expression. p62 regulates multiple signaling pathways including those that control autophagy, apoptosis, and tumorigenesis through its different domains (Fan, Yin, Zhang, & Hu, ; Islam, Sooro, & Zhang, ). Autophagy induction induces an increase in LC3‐II and a concurrent decrease in p62 (Yoshii & Mizushima, ).…”

Section: Resultsmentioning

confidence: 99%

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Tseng

Chiou

Weng

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

Most anticancer agents induce cancer cell death; however, multidrug-resistant cancers often lead to treatment failure. The effective use of curcumin as an anticancer agent has been demonstrated in clinical trials. Tetrahydrocurcumin, a major curcumin metabolite, exhibits pharmacological activities similar to those of curcumin. Curcumin induces cell death mainly through the apoptosis pathway, and tetrahydrocurcumin induces cell death mainly via an autophagy pathway in HL60 cells. Here, we investigated whether curcumin and tetrahydrocurcumin can induce apoptosis-and autophagy-mediated cell deaths in Ara-C-resistant cancer cells, respectively. The results demonstrated that curcumin and tetrahydrocurcumin induced cell death by apoptosis and autophagy, respectively, in Ara-C-resistant HL60 cells. Thus, curcumin and tetrahydrocurcumin have potential applications in the treatment of acute myeloid leukemia with Ara-C resistance.

show abstract

“…While LC3-I remains in the cytosol, LC3-II is incorporated into both the outer and the inner membrane of the autophagosome, and therefore LC3-II is largely considered as a marker of autophagy induction [54]. Also, an adaptor protein sequestosome 1 (SQTM1, known as p62), which directs substrates to the autophagosomes, is degraded with its cargo proteins and can be used as a read-out of the autophagic flux [58,59]. Another conjugation system is under control of ATG7 and ATG10, and regulates the formation of the ATG5/ATG12 conjugate.…”

Section: An Overview Of Autophagy and Autophagy-dependent Cell Deathmentioning

confidence: 99%

Non-Apoptotic Cell Death Signaling Pathways in Melanoma

Hartman

2020

IJMS

View full text Add to dashboard Cite

Resisting cell death is a hallmark of cancer. Disturbances in the execution of cell death programs promote carcinogenesis and survival of cancer cells under unfavorable conditions, including exposition to anti-cancer therapies. Specific modalities of regulated cell death (RCD) have been classified based on different criteria, including morphological features, biochemical alterations and immunological consequences. Although melanoma cells are broadly equipped with the anti-apoptotic machinery and recurrent genetic alterations in the components of the RAS/RAF/MEK/ERK signaling markedly contribute to the pro-survival phenotype of melanoma, the roles of autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and parthanatos have recently gained great interest. These signaling cascades are involved in melanoma cell response and resistance to the therapeutics used in the clinic, including inhibitors of BRAF mut and MEK1/2, and immunotherapy. In addition, the relationships between sensitivity to non-apoptotic cell death routes and specific cell phenotypes have been demonstrated, suggesting that plasticity of melanoma cells can be exploited to modulate response of these cells to different cell death stimuli. In this review, the current knowledge on the non-apoptotic cell death signaling pathways in melanoma cell biology and response to anti-cancer drugs has been discussed.

show abstract

Autophagic Regulation of p62 is Critical for Cancer Therapy

Cited by 189 publications

References 100 publications

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Non-Apoptotic Cell Death Signaling Pathways in Melanoma

Contact Info

Product

Resources

About