Epithelial-mesenchymal transition as a therapeutic target for overcoming chemoresistance in pancreatic cancer

Elaskalani, Omar; Razak, Norbaini Binti Abdol; Falasca, Marco; Metharom, Pat

doi:10.4251/wjgo.v9.i1.37

Cited by 54 publications

(38 citation statements)

References 32 publications

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“…The viewpoint was supported by the findings in the study by Ren et al, who suggested that targeted inhibition of ZEBl in pancreatic cells can restore epithelial cell characteristics, and enhance the sensitivity of antitumor drugs. Moreover, recent clinical studies have shown that EMT‐targeted therapeutic strategies can reverse cancer resistance to the chemotherapeutic drug, including carboplatin and gemcitabine …”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Inhibition of Notch1 reverses EMT and chemoresistance to cisplatin via direct downregulation of MCAM in triple‐negative breast cancer cells

Zeng

Liang

Xiao

et al. 2020

Intl Journal of Cancer

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Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple-negative breast cancer (TNBC). Epithelial-mesenchymal transition (EMT) is thought to contribute to chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal-like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA-MB-231 cells gradually increases in a time-dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatinresistant MDA-MB-231 cells are significantly higher than wild-type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC. D.Z. and Y.-K.L. contributed equally to this work Additional Supporting Information may be found in the online version of this article.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Inhibition of Notch1 reverses EMT and chemoresistance to cisplatin via direct downregulation of MCAM in triple‐negative breast cancer cells

Zeng

Liang

Xiao

et al. 2020

Intl Journal of Cancer

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“…found that the expression of p21 is up‐regulated and phosphorylated (p‐) AKT is down‐regulated through inhibition of Skp2, thereby preventing the progression of tumour. EMT is considered to be closely related to invasion and metastasis of gliomas . The activation of EMT involves various molecular and signal transduction pathways.…”

Section: Anticancer Activities Of Paeoniflorin and Its Potential Mechmentioning

confidence: 99%

“…EMT is considered to be closely related to invasion and metastasis of gliomas. [64][65][66][67] The activation of EMT involves various molecular and signal transduction pathways. It has been proved that transforming growth factor-b (TGF-b) and MMP2/9 are a kind of key cytokine, which are closely related to the invasion, proliferation and angiogenesis of gliomas.…”

Section: Colorectal Cancermentioning

confidence: 99%

Paeoniflorin: a monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities

Xiang

Zhang

Wei

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Paeoniflorin, a representative pinane monoterpene glycoside in plants of Paeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancers in vivo and in vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations. Key findings Anticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential molecular mechanisms corresponding to the antitumour effects of Paeoniflorin might be related to the following aspects: inhibition of tumour cell proliferation and neovascularization, induction apoptosis, and inhibition of tumour invasion and metastasis. Summary Paeoniflorin has wide spectrum antitumour activities; however, in vivo and clinical investigations on antitumour effect of Paeoniflorin are lacking which should be focused on further studies. Our present review on antitumour effects of Paeoniflorin would be beneficial for the further molecular mechanisms study, candidate antitumour drug development and clinical research of Paeoniflorin in the future.

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“…Thus, since the EMT process is crucial for cancer-enhanced invasion, metastasis, chemoresistance, and survival, it is now the target of different experimental therapeutic approaches [3][4][5]. However, even though the role of EMT in the pathogenesis of cancer transformation has been proven in vitro and in vivo, its translation to the clinic has failed in most cases.…”

Section: Specificities Of Tumor Emtmentioning

confidence: 99%

“…In this sense, there is growing evidence suggesting that targeting EMT can be used as a therapeutic approach itself, or to enhance the efficacy of other anticancer treatments [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment

Cordani

Strippoli

Somoza

2019

Cancers

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Epithelial-mesenchymal transition (EMT) has emerged as a key regulator of cell invasion and metastasis in cancers. Besides the acquisition of migratory/invasive abilities, the EMT process is tightly connected with the generation of cancer stem cells (CSCs), thus contributing to chemoresistance. However, although EMT represents a relevant therapeutic target for cancer treatment, its application in the clinic is still limited due to various reasons, including tumor-stage heterogeneity, molecular-cellular target specificity, and appropriate drug delivery. Concerning this last point, different nanomaterials may be used to counteract EMT induction, providing novel therapeutic tools against many different cancers. In this review, (1) we discuss the application of various nanomaterials for EMT-based therapies in cancer, (2) we summarize the therapeutic relevance of some of the proposed EMT targets, and (3) we review the potential benefits and weaknesses of each approach.

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Epithelial-mesenchymal transition as a therapeutic target for overcoming chemoresistance in pancreatic cancer

Cited by 54 publications

References 32 publications

RETRACTED: Inhibition of Notch1 reverses EMT and chemoresistance to cisplatin via direct downregulation of MCAM in triple‐negative breast cancer cells

RETRACTED: Inhibition of Notch1 reverses EMT and chemoresistance to cisplatin via direct downregulation of MCAM in triple‐negative breast cancer cells

Paeoniflorin: a monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities

Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment

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