HMGB1-mediated autophagy attenuates gemcitabine-induced apoptosis in bladder cancer cells involving JNK and ERK activation

Yin, Hubin; Yang, Xiaoyu; Gu, Wen; Liu, Yan; Li, Xinyuan; Huang, Xiaolong; Zhu, Xin; Tao, Yong; Gou, Xin; He, Weiyang

doi:10.18632/oncotarget.17796

Cited by 64 publications

(57 citation statements)

References 55 publications

(41 reference statements)

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“…31,32 Our data suggest that inhibition of autophagy can also inhibit the invasion and migration of bladder cancer cells, thereby providing a new theoretical basis for the prevention of bladder cancer invasion and migration and highlighting the importance of inhibiting autophagy in the treatment of bladder cancer. Furthermore, autophagy and TGF-β1 can form a positive feedback loop, which enhances the invasion and migration of T24 and 5637 cells by synergistic promoting EMT-mediated by the TGF-β1/Smad3 signaling pathway.…”

Section: F I G U R E 3 Autophagy Promotes the Invasion And Migration mentioning

confidence: 80%

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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Section: F I G U R E 3 Autophagy Promotes the Invasion And Migration mentioning

confidence: 80%

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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“…Therefore, we will not discuss this hypothesis in the present review; rather, we will focus on newly emerging molecular mechanisms in this context. Recent studies have proposed potential molecular mechanisms underlying the prosurvival function of JNK, including autophagy . JNK can induce autophagy and counteract cancer cell apoptosis .…”

Section: Mechanisms By Which Jnk Regulates Cancer Cell Survivalmentioning

confidence: 99%

“…During mesenchymal stem cells (MSCs) transplantation, JNK‐mediated autophagy counteracts apoptosis to prolong MSC survival . Although GEM kills bladder cancer cells by inducing apoptosis, the cytotoxicity of GEM is counteracted by the JNK‐mediated activation of autophagy . Autophagy‐dependent JNK activity also promotes gastric cancer cell survival through maintaining the normal function of mitochondria …”

Section: Mechanisms By Which Jnk Regulates Cancer Cell Survivalmentioning

confidence: 99%

“…Nuclear factor kappa B (NF‐κB), p38, and JNK share common upstream activators and may act synergistically to regulate cancer cell survival . The role of JNK in promoting cancer cell survival involves autophagy, as JNK can induce autophagy to counteract apoptosis . Extensive evidence supports that JNK‐mediated prosurvival autophagy promotes cancer cell resistance to chemotherapy, and recent studies suggest the involvement of tumor immune evasion in this process .…”

Section: Introductionmentioning

confidence: 99%

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JNK signaling in cancer cell survival

et al. 2019

Medicinal Research Reviews

219

146

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c‐Jun N‐terminal kinase (JNK) is involved in cancer cell apoptosis; however, emerging evidence indicates that this Janus signaling promotes cancer cell survival. JNK acts synergistically with NF‐κB, JAK/STAT, and other signaling molecules to exert a survival function. JNK positively regulates autophagy to counteract apoptosis, and its effect on autophagy is related to the development of chemotherapeutic resistance. The prosurvival effect of JNK may involve an immune evasion mechanism mediated by transforming growth factor‐β, toll‐like receptors, interferon‐γ, and autophagy, as well as compensatory JNK‐dependent cell proliferation. The present review focuses on recent advances in understanding the prosurvival function of JNK and its role in tumor development and chemoresistance, including a comprehensive analysis of the molecular mechanisms underlying JNK‐mediated cancer cell survival. There is a focus on the specific “Yin and Yang” functions of JNK1 and JNK2 in the regulation of cancer cell survival. We highlight recent advances in our knowledge of the roles of JNK in cancer cell survival, which may provide insight into the distinct functions of JNK in cancer and its potential for cancer therapy.

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“…Increasing evidence indicates that autophagy can prolong the survival of cancer cells and enhance their resistance to apoptosis [27, 28]. Because the manipulation of autophagy may improve the efficacy of anticancer therapeutics, we were eager to assess the effect of salidroside-elicited autophagy on the survival of SW1353 cells.…”

Section: Resultsmentioning

confidence: 99%

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells

Zeng

Xiao

Cai

et al. 2017

Cell Physiol Biochem

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Background/Aims: Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. Methods: We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. Results: We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB ^(Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. Conclusions: These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells.

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HMGB1-mediated autophagy attenuates gemcitabine-induced apoptosis in bladder cancer cells involving JNK and ERK activation

Cited by 64 publications

References 55 publications

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

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

JNK signaling in cancer cell survival

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells

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