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  3. Extracellular vesicles microRNA-592 of melanoma stem cells promotes metastasis through activation of MAPK/ERK signaling pathway by targeting PTPN7 in non-stemness melanoma cells

Extracellular vesicles microRNA-592 of melanoma stem cells promotes metastasis through activation of MAPK/ERK signaling pathway by targeting PTPN7 in non-stemness melanoma cells

  • Cell Death Discov. 2022 Oct 27;8(1):428. doi: 10.1038/s41420-022-01221-z.
Yuhan Zhang 1 2,  Yan Chen 1 2,  Lei Shi 1 2,  Jie Li 3,  Wenjuan Wan 4,  Bowen Li 1 2,  Doudou Liu 1 2,  Xiaoshuang Li 1 2,  Yuting Chen 1 2,  Meng Xiang 1 2,  Hao Chen 1 2,  Bin Zeng 3,  H Rosie Xing 5 6 7,  Jianyu Wang 8 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, 400016, Chongqing, China.
  • 2 Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, 400016, Chongqing, China.
  • 3 Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
  • 4 Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, China.
  • 5 State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, 400016, Chongqing, China. [email protected].
  • 6 Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, 400016, Chongqing, China. [email protected].
  • 7 Chongqing Medical University, Yi Xue Yuan Road, Yuzhong District, 400016, Chongqing, P.R. China. [email protected].
  • 8 Institute of Life Sciences, Chongqing Medical University, Chongqing, China. [email protected].
  • 9 Chongqing Health Center for Women and Children, Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China. [email protected].
  • 10 Chongqing Medical University, Yi Xue Yuan Road, Yuzhong District, 400016, Chongqing, P.R. China. [email protected].
PMID: 36302748 DOI: 10.1038/s41420-022-01221-z
Abstract

Melanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous Cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative Cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel MicroRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine Phosphatase non-receptor type7 (PTPN7), a Phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.

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