Autophagy in cancer: a complex relationship

Wilde, Lindsay; Tanson, Katherina; Curry, Joseph; Martinez‐Outschoorn, Ubaldo

doi:10.1042/bcj20170847

Cited by 54 publications

(56 citation statements)

References 214 publications

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“…In 2011, the idea of “autophagy addiction” was proposed as a promising therapeutic approach for certain tumours . In reality, autophagy plays different roles in cancer biology, depending on the tumour type and the context . In OSCC, various studies have drawn inconsistent conclusions regarding the associations between the levels of autophagy‐related proteins and a poor prognosis …”

Section: Introductionmentioning

confidence: 99%

“…6 In reality, autophagy plays different roles in cancer biology, depending on the tumour type and the context. 7 In OSCC, various studies have drawn inconsistent conclusions regarding the associations between the levels of autophagy-related proteins and a poor prognosis. 8,9 Autophagy initiation is controlled through unc-51-like kinase-1 (ULK1) and vacuolar protein sorting-34 (VPS34).…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma

Yin

Feng

et al. 2019

J Oral Pathology Medicine

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Background The aim of this study was to conduct a comparative evaluation of the expression levels of autophagy markers and proteins of the mammalian target of rapamycin (mTOR) pathway in normal, margin and tumour tissues of patients with oral squamous cell carcinoma (OSCC). Materials and Methods Three regional specimens, including normal, margin and tumour tissues, were collected from 26 patients with OSCC. Western blotting, immunohistochemistry and immunofluorescence staining were performed to detect mTOR, eukaryotic translation initiation factor 4E‐binding protein 1 (4E‐BP1), p70 ribosomal S6 protein kinase (p70S6K) and the corresponding phosphorylated proteins, as well as the light chain 3 (LC3) and sequestosome‐1 (SQSTM1, also known as p62) autophagy indicators. Results LC3‐II, p62, mTOR, phospho‐mTOR, 4E‐BP1 and phospho‐4E‐BP1 were highly expressed in the margin and tumour groups. There were positive correlations between mTOR/phospho‐mTOR, mTOR/4E‐BP1, mTOR/phospho‐4E‐BP1, mTOR/p70S6K, LC3‐II/p62, LC3‐II/p70S6K, p62/4E‐BP1 and p62/phospho‐4E‐BP1 in normal group, while LC3‐II/p62, LC3‐II/mTOR, LC3‐II/4E‐BP1, LC3‐II/phospho‐4E‐BP1, phospho‐4E‐BP1/mTOR, phospho‐4E‐BP1/4E‐BP1 and p62/4E‐BP1 showed positive relationships in margin group; however, in tumour group, only mTOR/phospho‐mTOR, 4E‐BP1/phospho‐4E‐BP1 and phospho‐mTOR/p70S6K showed positive correlations. Conclusion The study suggests that autophagy is impaired in patients with OSCC and impaired autophagy and the mTOR pathway are simultaneously activated in OSCC cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma

Yin

Feng

et al. 2019

J Oral Pathology Medicine

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“…5,6 In addition, nutritional deficiency can induce autophagy. 9 Autophagy plays a central role in the formation, growth, invasion, and migration of tumors. 9 Autophagy plays a central role in the formation, growth, invasion, and migration of tumors.…”

Section: Introductionmentioning

confidence: 99%

Starvation‐induced autophagy promotes the invasion and migration of human bladder cancer cells via TGF‐β1/Smad3‐mediated epithelial‐mesenchymal transition activation

Tong

Yin

Hossain

et al. 2018

J of Cellular Biochemistry

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The biological characteristics of bladder cancer include enhanced invasion and migration, which are the main causes of death in patients. Starvation is a typical feature of the bladder cancer microenvironment and can induce autophagy. Autophagy has an important relationship with the invasion and migration of tumors. However, the role of autophagy in the invasion and migration of bladder cancer cells remains unclear. Hence, the aim of the current study was to clarify this role and underlying mechanism. In this study, we found that starvation enhanced the epithelial‐mesenchymal transition (EMT)‐mediated invasion and migration of T24 and 5637 cells while inducing autophagy. The inhibition of autophagy with chloroquine (CQ) or 3‐methyladenine (3MA) decreased EMT‐mediated invasion and migration. In addition, the expression of transforming growth factor 1 (TGF‐β1) and phosphorylated Smad3 (p‐Smad3) increased after starvation. The inhibition of autophagy with CQ or 3MA also decreased the expression of TGF‐β1 and p‐Smad3. The inhibitor of TGF‐β receptor sb431542 also inhibited the invasion, migration, and EMT of T24 and 5637 cells during starvation. Furthermore, recombinant TGF‐β1 induced autophagy and inhibition of the TGF‐β/Smad signaling pathway with sb431542 suppressed autophagy. In summary, our results suggested that autophagy promotes the invasion and migration of bladder cancer cells by inducing EMT through the TGF‐β1/Smad3 signaling pathway. Moreover, autophagy and TGF‐β1 can form a positive feedback loop to synergistically promote invasion and migration. Thus, our findings may provide a theoretical basis for the prevention of invasion and migration in bladder cancer.

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“…Autophagy describes the fundamental catabolic mechanism during which cells degrade dysfunctional and unnecessary cellular components (41,42). This process is driven by the action of lysosomes and promotes survival during starvation periods, as the cellular energy level can thus be maintained (42). In this study, RSF did not induce the autophagy (data not shown), but the apoptosis.…”

Section: Apoptosis Can Be Initiated Via Two Signalling Pathwaysmentioning

confidence: 48%

“…Apoptosis involves a complex cascade of reactions regulated by specific proteases called caspases, and results in DNA degradation (34). Autophagy describes the fundamental catabolic mechanism during which cells degrade dysfunctional and unnecessary cellular components (41,42). This process is driven by the action of lysosomes and promotes survival during starvation periods, as the cellular energy level can thus be maintained (42).…”

Section: Apoptosis Can Be Initiated Via Two Signalling Pathwaysmentioning

confidence: 99%

Radix Sophorae Flavescentis inhibits proliferation and induces apoptosis of AGS human gastric cancer cells

et al. 2018

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Traditional herbal medicines are being increasingly used worldwide to treat cancer. Radix Sophorae Flavescentis (RSF) is a Chinese herb, which has numerous pharmacological properties, including anti-tumour effects. In this study, we investigated the mechanisms underlying RSF-induced apoptosis in human gastric cancer cells (AGS cells). We found that RSF treatment (20-200 µg/ml) inhibited the proliferation of AGS cells and increased the sub-G1 phase ratio. RSF-induced cell death was associated with the downregulation of BCl-2 and upregulation of Bax. In addition to increasing the expression levels of apoptosis-mediating surface antigen FAS and Fas ligand, RSF also activated caspase-3; however, mitogen-activated protein kinase appeared to inhibit RSF-induced cell death. RSF also led to an increased production of reactive oxygen species. Based on these results, we propose that RSF could be a potential therapeutic agent for gastric cancer.

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Autophagy in cancer: a complex relationship

Cited by 54 publications

References 214 publications

Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma

Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma

Starvation‐induced autophagy promotes the invasion and migration of human bladder cancer cells via TGF‐β1/Smad3‐mediated epithelial‐mesenchymal transition activation

Radix Sophorae Flavescentis inhibits proliferation and induces apoptosis of AGS human gastric cancer cells

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