ERas Enhances Resistance to Cisplatin-Induced Apoptosis by Suppressing Autophagy in Gastric Cancer Cell

Tian, Huajian; Wang, Wenjun; Meng, Xiao; Wang, Miaomiao; Tan, Junyang; Jia, Wenhao; Li, Peining; Li, Jianshuang; Zhou, Qinghua

doi:10.3389/fcell.2019.00375

Cited by 12 publications

(8 citation statements)

References 31 publications

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“…Autophagy has been suggested to play controversial roles in cancer therapy. In some cases, autophagy is confirmed to have cytoprotective effects on the survival of cancer cells, and autophagy inhibition could potentiate the sensitivity of cancer cells to anticancer drugs, such as cisplatin and doxorubicin (Li et al, 2017;Xu et al, 2017;Tian et al, 2019). However, more evidences reveal that autophagy activation could promote cancer cell death (Denton and Kumar, 2019;Kriel and Loos, 2019).…”

Section: Discussionmentioning

confidence: 99%

PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways

Mei

Yang

et al. 2021

Front. Pharmacol.

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PPM-18, identified as a novel analog of vitamin K, has been reported to play a critical role in the suppression of seizures. However, the concerns that whether PPM-18, like vitamin K, exerts anticancer activity remain to be further investigated. Here, we found that PPM-18 remarkably suppressed the proliferation and induced apoptosis in bladder cancer cells. Furthermore, a significant autophagic effect of PPM-18 on bladder cancer cells was also demonstrated, which profoundly promoted apoptotic cell death. Mechanistically, PPM-18 activated AMP-activated protein kinase (AMPK), whereas it repressed PI3K/AKT and mTORC1 pathways in bladder cancer cells. Inhibition of AMPK markedly relieved PPM-18–induced autophagy and apoptosis, indicating that PPM-18 is able to induce autophagy and apoptosis in bladder cancer cells via AMPK activation. Moreover, reactive oxygen species (ROS) were notably accumulated in PPM-18–treated bladder cancer cells, and treatment with ROS scavengers not only eliminated ROS production but also abrogated AMPK activation, which eventually rescued bladder cancer cells from PPM-18–triggered autophagy and apoptotic cell death. In bladder cancer xenografts, the anticancer activities of PPM-18, including suppressing the growth of tumors and inducing autophagy and apoptosis in tumor cells, were also established. Collectively, this study was the first to demonstrate the anticancer effect of PPM-18 on bladder cancer cells in vitro and in vivo through eliciting autophagy and apoptosis via ROS and AMPK pathways, which might provide new insights into the potential utilization of PPM-18 for future bladder cancer treatment.

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Section: Discussionmentioning

confidence: 99%

PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways

Mei

Yang

et al. 2021

Front. Pharmacol.

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“…Moreover, after this treatment, an increase in astrocytic (GFAP; Glial Fibrillary Acidic Protein) and neuronal (TUBB3; Tubulin Beta 3 class III) differentiation markers in GSCs was revealed. This autophagy-mediated differentiation has been highlighted in some other cancer types, including colon, liver and gastric cancers [81][82][83]. A 2019 study [84] demonstrated both in vitro and in vivo that metformin, a common drug used to treat type II diabetes, could suppress the self-renewal and tumorigenicity abilities of Osteosarcoma Stem Cells (OSCs).…”

Section: Rab Family Autophagy and Cscsmentioning

confidence: 99%

Autophagy and Extracellular Vesicles, Connected to rabGTPase Family, Support Aggressiveness in Cancer Stem Cells

Brunel

Bégaud-Grimaud

Auger

et al. 2021

Cells

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Even though cancers have been widely studied and real advances in therapeutic care have been made in the last few decades, relapses are still frequently observed, often due to therapeutic resistance. Cancer Stem Cells (CSCs) are, in part, responsible for this resistance. They are able to survive harsh conditions such as hypoxia or nutrient deprivation. Autophagy and Extracellular Vesicles (EVs) secretion are cellular processes that help CSC survival. Autophagy is a recycling process and EVs secretion is essential for cell-to-cell communication. Their roles in stemness maintenance have been well described. A common pathway involved in these processes is vesicular trafficking, and subsequently, regulation by Rab GTPases. In this review, we analyze the role played by Rab GTPases in stemness status, either directly or through their regulation of autophagy and EVs secretion.

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“…Embryonic stem cell-expressed Ras (ERas) is a novel member of the Ras protein family and is highly expressed in gastric, colorectal, and breast cancer ( Suárez-Cabrera et al, 2018 ; Tian et al, 2019 ). Tian et al (2019) have found that ERas overexpression significantly increases the phosphorylation level of mTOR (Ser2448) and its substrate (ULK1-Ser757), as well as AKT-Ser473, activates the AKT/mTOR pathway, blocks autophagic flux in gastric cancer cells, suppresses DDP-induced apoptosis, and induces DDP resistance. In contrast, silencing ERas has been found to increase autophagic flux and enhance the sensitivity of gastric cancer cells to DDP in vitro ( Tian et al, 2019 ).…”

Section: Dual Roles Of Autophagy In Chemoresistance Of Gastric Cancermentioning

confidence: 99%

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

Tang

et al. 2020

Front. Cell Dev. Biol.

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Gastric cancer is the third most common cause of cancer-related death worldwide. Drug resistance is the main inevitable and vital factor leading to a low 5-year survival rate for patients with gastric cancer. Autophagy, as a highly conserved homeostatic pathway, is mainly regulated by different proteins and non-coding RNAs (ncRNAs) and plays dual roles in drug resistance of gastric cancer. Thus, targeting key regulatory nodes in the process of autophagy by small molecule inhibitors or activators has become one of the most promising strategies for the treatment of gastric cancer in recent years. In this review, we provide a systematic summary focusing on the relationship between autophagy and chemotherapy resistance in gastric cancer. We comprehensively discuss the roles and molecular mechanisms of multiple proteins and the emerging ncRNAs including miRNAs and lncRNAs in the regulation of autophagy pathways and gastric cancer chemoresistance. We also summarize the regulatory effects of autophagy inhibitor and activators on gastric cancer chemoresistance. Understanding the vital roles of autophagy in gastric cancer chemoresistance will provide novel opportunities to develop promising therapeutic strategies for gastric cancer.

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ERas Enhances Resistance to Cisplatin-Induced Apoptosis by Suppressing Autophagy in Gastric Cancer Cell

Cited by 12 publications

References 31 publications

PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways

PPM-18, an Analog of Vitamin K, Induces Autophagy and Apoptosis in Bladder Cancer Cells Through ROS and AMPK Signaling Pathways

Autophagy and Extracellular Vesicles, Connected to rabGTPase Family, Support Aggressiveness in Cancer Stem Cells

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

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