ATG7-dependent and independent autophagy determine the type of treatment in lung cancer

Zhang, Pinghu; Li, Ling; Zheng, Zu-Guo; Zhang, Yuqian; Wang, Ronghua; Wu, Min; Zhang, Ni; Hu, Mengjie; Yang, Xiaohui

doi:10.1016/j.phrs.2020.105324

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…Conversely, Holah S. et al demonstrated that Beclin-1 was upregulated in prostatic cancer and is associated with poor prognostic factors [ 163 ]. Other ATGs including ATG5, ATG7 and FIP200 were linked to human cancers [ 164 , 165 , 166 ]. Furthermore, recent evidence revealed that six polymorphisms ATG2B rs3759601, ATG16L1 rs2241880, ATG10 rs1864183, NOD2 rs2066844 and rs2066845 and ATG5 rs2245214 were associated with a predisposition to tumor development, particularly in glioblastoma [ 167 ].…”

Section: Autophagy and Its Dual Role In The Regulation Of Cancermentioning

confidence: 99%

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

et al. 2022

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Autophagy is an evolutionarily conserved and tightly regulated process that plays an important role in maintaining cellular homeostasis. It involves regulation of various genes that function to degrade unnecessary or dysfunctional cellular components, and to recycle metabolic substrates. Autophagy is modulated by many factors, such as nutritional status, energy level, hypoxic conditions, endoplasmic reticulum stress, hormonal stimulation and drugs, and these factors can regulate autophagy both upstream and downstream of the pathway. In cancer, autophagy acts as a double-edged sword depending on the tissue type and stage of tumorigenesis. On the one hand, autophagy promotes tumor progression in advanced stages by stimulating tumor growth. On the other hand, autophagy inhibits tumor development in the early stages by enhancing its tumor suppressor activity. Moreover, autophagy drives resistance to anticancer therapy, even though in some tumor types, its activation induces lethal effects on cancer cells. In this review, we summarize the biological mechanisms of autophagy and its dual role in cancer. In addition, we report the current understanding of autophagy in some cancer types with markedly high incidence and/or lethality, and the existing therapeutic strategies targeting autophagy for the treatment of cancer.

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Section: Autophagy and Its Dual Role In The Regulation Of Cancermentioning

confidence: 99%

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

et al. 2022

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“…For example, ATG7-dependent autophagy suppressed the progression of lung cancer driven by activation of oncogenic HRasV12 [ 22 ]. In contrast to the tumour suppressive effect of ATG7 on tumour development [ 23 ], blockage by ATG7 deficiency contributed to promoting the sensitivity to chemotherapy in resistant cells [ 24 ]. Interestingly, we found that silencing ATG7 also accelerated lung tumour apoptosis induced by icotinib, suggesting the importance of ATG7 in autophagy-dependent resistance to icotinib.…”

Section: Discussionmentioning

confidence: 99%

Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib

Lyu

Zeng

Shi

et al. 2022

J Exp Clin Cancer Res

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Background The contribution of autophagy to cancer therapy resistance remains complex, mainly owing to the discrepancy of autophagy mechanisms in different therapy. However, the potential mechanisms of autophagy-mediated resistance to icotinib have yet to be elucidated. Methods The effect of autophagy in icotinib resistance was examined using a series of in vitro and in vivo assays. The results above were further verified in biopsy specimens of lung cancer patients before and after icotinib or gefitinib treatment. Results Icotinib increased ATG3, ATG5, and ATG7 expression, but without affecting Beclin-1, VPS34 and ATBG14 levels in icotinib-resistant lung cancer cells. Autophagy blockade by 3-MA or silencing Beclin-1 had no effects on resistance to icotinib. CQ effectively restored lung cancer cell sensitivity to icotinib in vitro and in vivo. Notably, aberrantly activated STAT3 and highly expressed FOXM1 were required for autophagy induced by icotinib, without the involvement of AMPK/mTOR pathway in this process. Alterations of STAT3 activity using genetic and/or pharmacological methods effectively affected FOXM1 and ATG7 levels increased by icotinib, with altering autophagy and icotinib-mediated apoptosis in resistant cells. Furthermore, silencing FOXM1 impaired up-regulated ATG7 induced by STAT3-CA and icotinib. STAT3/FOXM1 signalling blockade also reversed resistance to icotinib in vivo. Finally, we found a negative correlation between STAT3/FOXM1/ATG7 signalling activity and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment efficacy in patients undergoing EGFR-TKIs treatment. Conclusions Our findings support that STAT3/FOXM1/ATG7 signalling-induced autophagy is a novel mechanism of resistance to icotinib, and provide insights into potential clinical values of ATG7-dependent autophagy in icotinib treatment. Graphical abstract

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“…Atg5-independent autophagy has also been described in cells from fetal brains, livers, and hearts [47], as well as in human epidermis [51]. In addition to normal cells, alternative autophagy has also been reported in various cancer cell lines, including prostate DU145 cancer cells [54,55], erythroleukemia K562 cells [6], adenocarcinoma H1650 cells, and lung carcinoma A549 cells [56].…”

Section: Alternative Autophagy-a Short Overviewmentioning

confidence: 94%

The Secrets of Alternative Autophagy

Urbańska

Orzechowski

2021

Cells

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For many years, it was thought that ATG5 and ATG7 played a pivotal role in autophagy, and that the knockdown of one of these genes would result in its inhibition. However, cells with ATG5 or ATG7 depletion still generate autophagic vacuoles with mainly trans-Golgi-originated isolation membranes and do not die. This indicates that autophagy can occur via ATG5/ATG7-independent alternative autophagy. Its molecular mechanism differs from that of the canonical pathway, including inter alia the phosphorylation of ULK1, and lack of LC3 modifications. As the alternative autophagy pathway has only recently been described, little is known of its precise role; however, a considerable body of evidence suggests that alternative autophagy participates in mitochondrion removal. This review summarizes the latest progress made in research on alternative autophagy and describes its possible molecular mechanism, roles and methods of detection, and possible modulators. There is a need for further research focused on types of autophagy, as this can elucidate the functioning of various cell types and the pathogenesis of human and animal diseases.

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ATG7-dependent and independent autophagy determine the type of treatment in lung cancer

Cited by 13 publications

References 30 publications

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib

The Secrets of Alternative Autophagy

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