The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer

Zhou, Pingting; Li, Bo; Liu, Fu-Rao; Zhang, Meichao; Wang, Qian; Liu, Yuanhua; Yuan, Yao; Liu, Dong

doi:10.1186/s12943-017-0624-9

Cited by 259 publications

(196 citation statements)

References 132 publications

(133 reference statements)

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“…These findings indicate that the formation of cisplatin resistance is associated with EMT. Numerous studies have shown that EMT plays an important role in the progression, invasion, metastasis and drug resistance of a variety of cancers including GC . In this study, E‐cadherin expression was down‐regulated and vimentin expression was up‐regulated in GC cells treated with cisplatin, indicating that GC cells treated with cisplatin experienced EMT‐like changes.…”

Section: Discussionmentioning

confidence: 54%

Cisplatin resistance in gastric cancer cells is involved with GPR30‐mediated epithelial‐mesenchymal transition

Wang

Sun

et al. 2020

J Cellular Molecular Medi

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Cisplatin is the major chemotherapeutic drug in gastric cancer, particularly in treating advanced gastric cancer. Tumour cells often develop resistance to chemotherapeutic drugs, which seriously affects the efficacy of chemotherapy. GPR30 is a novel oestrogen receptor that is involved in the invasion, metastasis and drug resistance of many tumours. Targeting GPR30 has been shown to increase the drug sensitivity of breast cancer cells. However, few studies have investigated the role of GPR30 in gastric cancer. Epithelial‐mesenchymal transition (EMT) has been shown to be associated with the development of chemotherapeutic drug resistance. In this study, we demonstrated that GPR30 is involved in cisplatin resistance by promoting EMT in gastric cancer. GPR30 knockdown resulted in increased sensitivity of different gastric cancer (GC) cells to cisplatin and alterations in the epithelial/mesenchymal markers. Furthermore, G15 significantly enhanced the cisplatin sensitivity of GC cells while G1 inhibited this phenomenon. In addition, EMT occurred when AGS and BGC‐823 were treated with cisplatin. Down‐regulation of GPR30 with G15 inhibited this transformation, while G1 promoted it. Taken together, these results revealed the role of GPR30 in the formation of cisplatin resistance, suggesting that targeting GPR30 signalling may be a potential strategy for improving the efficacy of chemotherapy in gastric cancer.

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Section: Discussionmentioning

confidence: 54%

Cisplatin resistance in gastric cancer cells is involved with GPR30‐mediated epithelial‐mesenchymal transition

Wang

Sun

et al. 2020

J Cellular Molecular Medi

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“…M2 macrophages are generally considered to be the phenotype of tumor-associated macrophages (TAMs), [454][455][456] have immunosuppressive and angiogenesis-promoting effects, and are considered to be a tumor-promoting cell type. 456,457 M2 macrophages secrete CCL17 (C-C chemokine ligand 17), CCL22, and CCL24 and have low expression of IL-12 and high expression of IL-10. Cytokines secreted by macrophages affect the proliferation, tumorigenic transformation, or apoptosis of CSCs through various signaling pathways.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,066

768

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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“…We revealed that resistance of EAC cells toward chemoradiation is mediated via EMT and increased stemness. Previous studies have shown that EMT is a critical regulator for acquiring and maintaining a subset of cells within the tumor, the cancer stem cell population . Indeed, cancer stem cells and cells that have undergone EMT are closely related in molecular and phenotypic characteristics.…”

Section: Discussionmentioning

confidence: 99%

Chemoradiation induces epithelial‐to‐mesenchymal transition in esophageal adenocarcinoma

Steins

Ebbing

Creemers

et al. 2019

Intl Journal of Cancer

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Multimodality treatment has advanced the outcome of esophageal adenocarcinoma (EAC), but overall survival remains poor. Therapeutic pressure activates effective resistance mechanisms and we characterized these mechanisms in response to the currently used neoadjuvant treatment against EAC: carboplatin, paclitaxel and radiotherapy. We developed an in vitro approximation of this regimen and applied it to primary patient‐derived cultures. We observed a heterogeneous epithelial‐to‐mesenchymal (EMT) response to the high therapeutic pressure exerted by chemoradiation. We found EMT to be initiated by the autocrine production and response to transforming growth factor beta (TGF‐β) of EAC cells. Inhibition of TGF‐β ligands effectively abolished chemoradiation‐induced EMT. Assessment of TGF‐β serum levels in EAC patients revealed that high levels after neoadjuvant treatment predicted the presence of fluorodeoxyglucose uptake in lymph nodes on the post‐chemoradiation positron emission tomography‐scan. Our study shows that chemoradiation contributes to resistant metastatic disease in EAC patients by inducing EMT via autocrine TGF‐β production. Monitoring TGF‐β serum levels during treatment could identify those patients at risk of developing metastatic disease, and who would likely benefit from TGF‐β targeting therapy.

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The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer

Cited by 259 publications

References 132 publications

Cisplatin resistance in gastric cancer cells is involved with GPR30‐mediated epithelial‐mesenchymal transition

Cisplatin resistance in gastric cancer cells is involved with GPR30‐mediated epithelial‐mesenchymal transition

Targeting cancer stem cell pathways for cancer therapy

Chemoradiation induces epithelial‐to‐mesenchymal transition in esophageal adenocarcinoma

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