The role of autophagy induced by tumor microenvironment in different cells and stages of cancer

Yang, Xue; Yu, Dandan; Yan, Fei; Jing, Yingying; Han, Zhipeng; Sun, Kai; Liang, Lei; Hou, Jing; Wei, Lixin

doi:10.1186/s13578-015-0005-2

Cited by 125 publications

(96 citation statements)

References 130 publications

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“…However, in most contexts autophagy facilitates tumorigenesis by helping cancer cells to adapt and survive microenvironmental stresses such as hypoxia, nutrient deprivation, and cancer treatment (i.g. chemotherapy and radiation therapy) [37]. Extensive in vitro and in vivo studies have demonstrated that modulation of autophagy can be used as a therapeutic modality to enhance the efficacy of various anticancer regimens [38].…”

Section: Discussionmentioning

confidence: 99%

MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

Chen

Zhou

Qiao

et al. 2017

Cell Physiol Biochem

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Background: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy. Methods: In the current study, we investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1-mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in vitro and in vivo. HMGB1 was identified as a putative target gene of miR-142-3p by in silico analysis. Our luciferase reporter assay results confirmed that miR-142-3p directly targets the 3’-UTR of HMGB1 in NSCLC cells. Results: MiR-142-3p overexpression suppressed while miR-142-3p knockdown increased HMGB1 mRNA and protein expression. Starvation induced HMGB1 expression and activated autophagy in NSCLC cells. The starvation-induced autophagy was inhibited by miR-142-3p overexpression or HMGB1 knockdown. Moreover, miR-142-3p overexpression or HMGB1 knockdown increased PI3K, Akt, and mTOR phosphorylation. Inhibition of PI3K or mTOR restored starvation-induced autophagy inhibited by miR-142-3p overexpression or HMGB1 knockdown. Conclusions: These results demonstrated that miR-142-3p regulates starvation-induced autophagy of NSCLC cells by directly downregulating HMGB1 and subsequently activating the PI3K/Akt/mTOR pathway. Further, miR-142-3p overexpression inhibited anticancer drug-induced autophagy and increased chemo-sensitivity of NSCLC in vitro and in vivo. These findings shed light on the therapeutic potential of miR-142-3p in combating acquired NSCLC chemo-resistance.

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Section: Discussionmentioning

confidence: 99%

MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

Chen

Zhou

Qiao

et al. 2017

Cell Physiol Biochem

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“…Descriptions of autophagy conceptualize a dual role within the context of cellular survival, either inducing programmed cell death type II or activating a pro-survival phenotype [19]. Autophagy can be activated by tumor microenvironments to protect hypoxic and nutrient deprived cells, thus inducing resistance to drug treatment [43]. The current study aimed to determine the role of autophagy associated demonstrated on cancer cell exposure to ESE-15-ol by inhibiting autophagy with 3MA.…”

Section: Discussionmentioning

confidence: 99%

Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells

et al. 2016

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Background Autophagy can either be protective and confer survival to stressed cells, or it can contribute to cell death. The antimitotic drug 2-ethyl-3-O-sulpamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) is an in silico-designed 17-β-estradiol analogue that induces both autophagy and apoptosis in cancer cells. The aim of the study was to determine the role of autophagy in ESE-15-ol-exposed human adenocarcinoma breast cancer cells; knowledge that will contribute to future clinical applications of this novel antimitotic compound. By inhibiting autophagy and determining the cytotoxic effects of ESE-15-ol-exposure, deductions could be made as to whether the process may confer resistance to the drug, or alternatively, contribute to the cell death process.Methods and results Spectophometrical analysis via crystal violet staining was used to perform cytotoxicity studies. Morphology studies were done using microscopic techniques namely polarization-optical transmitted light differential interference light microscopy, fluorescent microscopy using monodansylcadaverine staining and transmission electron microscopy. Flow cytometry was used to quantify the autophagy inhibition and assess cell viability. Results obtained indicated that 3-methyladenine inhibited autophagy and increased cell survival in both MCF-7 and MDA-MB-231 cell lines.ConclusionThis in vitro study inferred that autophagy inhibition with 3-methyladenine does not confer increased effectiveness of ESE-15-ol in inducing cell death. Thus it may be concluded that the autophagic process induced by ESE-15-ol exposure in MCF-7 and MDA-MB-231 cells plays a more significant role in cell death than conferring survival.

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“…However, recent studies found role of autophagy controversial either having pro-survival or pro-death role under various conditions at different stages of tumor cells. [12] …”

Section: Hypoxia-induced Autophagy Plays As Pro-survival or Pro-deathmentioning

confidence: 99%

“…[12] Having said as a solid tumor, HCC is more likely to experience starvation where autophagy counters this hypoxic stress in hepatocellular tumor spheroids. HIF-1α-induced BNIP3 expression led to enhanced HCC survival.…”

Section: Autophagy As a Survival Pathway For Hcc Under Hypoxiamentioning

confidence: 99%

“…[11] Increased autophagic activity is associated with 50%-60% of tumor cell survival under hypoxic conditions. [12] For example, hypoxia-induced autophagy promotes HCC cell survival [13] with malignant progression and poor prognosis. [14] Other types of solid tumors like colorectal, breast cancers [15,16] also experienced survival and aggressive phenotypes due to hypoxia-induced autophagy referring this phenomenon as a prosurvival factor for cancer.…”

Section: Autophagy Introductionmentioning

confidence: 99%

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Hypoxia-induced autophagy in hepatocellular carcinoma and anticancer therapy

Kabir¹,

Yong²

2017

Natl J Physiol Pharm Pharmacol

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Autophagy is a genetically programmed dynamic process for the lysosomal degradation and recycling of bulk cytoplasmic contents, abnormal proteins, and damaged organelles. Along with cellular homeostasis maintenance, autophagy plays a fundamental role in cancer as tumor cells activate autophagy under stressful conditions such as hypoxia, nutrient derivation, and anticancer therapy. Increasing reports suggest the protective role of autophagy in hepatocellular carcinoma (HCC). Despite recent developments in HCC anticancer treatment, the overall patient survival remains poor. Tumor hypoxia, a common characteristic of most solid tumors like HCC is correlated with poor prognosis for patients partly because hypoxia promotes resistance to cancer therapy. Hypoxia preferentially selects apoptosis-resistant cells and activates autophagy as a survival mechanism leading to malignant and aggressive phenotype. In this review, we summarized the molecules involved in hypoxia-induced autophagy for HCC progression and anticancer therapy resistance. In addition, the molecular pathways involved in hypoxia-induced autophagy were provided. We also focused on some recent researches between hypoxia-induced autophagy and microRNAs in HCC. We believe understanding the novel function of hypoxia-regulated autophagy may coin new targets for the betterment of HCC treatment and improved clinical outcomes.

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The role of autophagy induced by tumor microenvironment in different cells and stages of cancer

Cited by 125 publications

References 130 publications

MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells

Hypoxia-induced autophagy in hepatocellular carcinoma and anticancer therapy

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