Modification and Biological Evaluation of a Series of 1,5-Diaryl-1,2,4-triazole Compounds as Novel Agents against Pancreatic Cancer Metastasis through Targeting Myoferlin

Li, Yunqi; He, Yonghong; Shao, Ting; Pei, Haixiang; Guo, Weikai; Mi, Dazhao; Krimm, Isabelle; Zhang, Yuanjin; Wang, Peili; Wang, Xin; Liu, Mingyao; Yi, Zhengfang; Chen, Yi Hua

doi:10.1021/acs.jmedchem.9b00059

Cited by 30 publications

(28 citation statements)

References 29 publications

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“…Targeting myoferlin at the expression or functional levels remains, however, the next challenge. Interestingly, recent studies identified new small compounds interacting with the myoferlin C2D domain and demonstrating promising anti-tumoral/metastasis properties in breast and pancreas cancer [133,134].…”

Section: Discussionmentioning

confidence: 99%

Ferlin Overview: From Membrane to Cancer Biology

Peulen

Rademaker

Anania

et al. 2019

Cells

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In mammal myocytes, endothelial cells and inner ear cells, ferlins are proteins involved in membrane processes such as fusion, recycling, endo- and exocytosis. They harbour several C2 domains allowing their interaction with phospholipids. The expression of several Ferlin genes was described as altered in several tumoural tissues. Intriguingly, beyond a simple alteration, myoferlin, otoferlin and Fer1L4 expressions were negatively correlated with patient survival in some cancer types. Therefore, it can be assumed that membrane biology is of extreme importance for cell survival and signalling, making Ferlin proteins core machinery indispensable for cancer cell adaptation to hostile environments. The evidences suggest that myoferlin, when overexpressed, enhances cancer cell proliferation, migration and metabolism by affecting various aspects of membrane biology. Targeting myoferlin using pharmacological compounds, gene transfer technology, or interfering RNA is now considered as an emerging therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Ferlin Overview: From Membrane to Cancer Biology

Peulen

Rademaker

Anania

et al. 2019

Cells

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“…This molecule can reverse EMT of breast cancer and decrease pulmonary metastasis [63]. Another diaryl-1,2,4-triazole derived compound targeting MYOF also demonstrates potent antitumor effects similar to that of MYOF depletion [64]. Such MYOF-targeting compounds are expected to yield promising therapeutic benefits in the treatment of cancer.…”

Section: Role Of Myof In Cancermentioning

confidence: 99%

Myoferlin, a Membrane Protein with Emerging Oncogenic Roles

Dong

Kang

Liu

et al. 2019

BioMed Research International

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Myoferlin (MYOF), initially identified in muscle cells, is a member of the Ferlin family involved in membrane fusion, membrane repair, and membrane trafficking. Dysfunction of this protein is associated with muscular dysfunction. Recently, a growing body of studies have identified MYOF as an oncogenic protein. It is overexpressed in a variety of human cancers and promotes tumorigenesis, tumor cell motility, proliferation, migration, epithelial to mesenchymal transition, angiogenesis as well as metastasis. Clinically, MYOF overexpression is associated with poor outcome in various cancers. It can serve as a prognostic marker of human malignant disease. MYOF drives the progression of cancer in various processes, including surface receptor transportation, endocytosis, exocytosis, intercellular communication, fit mitochondrial structure maintenance and cell metabolism. Depletion of MYOF demonstrates significant antitumor effects both in vitro and in vivo, suggesting that targeting MYOF may produce promising clinical benefits in the treatment of malignant disease. In the present article, we reviewed the physiological function of MYOF as well as its role in cancer, thus providing a general understanding for further exploration of this protein.

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“…The anticancer activity of 6y is positively associated with the expression of myoferlin, and 6y is insensitive to myoferlin depletion. The specific mechanisms may be mediated by blocking the receptor tyrosine kinases, inhibiting the secretions of matrix metalloproteinase and reversing the EMT process . Overall, myoferlin may provide a novel therapeutic target in PAC.…”

Section: Roles Of Myoferlin In Cancersmentioning

confidence: 99%

“…39 The specific mechanisms may be mediated by blocking the receptor tyrosine kinases, inhibiting the secretions of matrix metalloproteinase and reversing the EMT process. 69 Overall, myoferlin may provide a novel therapeutic target in PAC.…”

Section: Myoferlin In Pancreatic Adenocarcinomamentioning

confidence: 99%

Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers

Zhu

Zhou

Zhao

et al. 2019

J Cellular Molecular Medi

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Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non‐small‐cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which mainly included promoting angiogenesis, vasculogenic mimicry, energy metabolism reprogramming, epithelial‐mesenchymal transition and modulating exosomes. The roles of myoferlin in both normal cells and cancer cells are of great significance to provide novel and efficient methods of tumour treatment. In this review, we summarize recent studies and findings of myoferlin and suggest that myoferlin is a novel potential candidate for clinical diagnosis and targeted cancer therapy.

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Modification and Biological Evaluation of a Series of 1,5-Diaryl-1,2,4-triazole Compounds as Novel Agents against Pancreatic Cancer Metastasis through Targeting Myoferlin

Cited by 30 publications

References 29 publications

Ferlin Overview: From Membrane to Cancer Biology

Ferlin Overview: From Membrane to Cancer Biology

Myoferlin, a Membrane Protein with Emerging Oncogenic Roles

Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers

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