Melanoma cell adhesion molecule is the driving force behind the dissemination of melanoma upon S100A8/A9 binding in the original skin lesion.

Animals CD146 Antigen / metabolism Calgranulin A / genetics Calgranulin B / genetics Cell Line, Tumor Cell Movement Cell Proliferation GPI-Linked Proteins / metabolism HEK293 Cells Humans Keratinocytes / pathology Lung Neoplasms / secondary MAP Kinase Kinase Kinases / metabolism Matrix Metalloproteinases, Membrane-Associated / metabolism Melanoma / pathology Melanoma, Experimental / pathology Mice Mice, Inbred BALB C Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-ets / metabolism RNA Interference RNA, Small Interfering / genetics Skin / pathology Skin Neoplasms / pathology Xenograft Model Antitumor Assays Melanoma, Cutaneous Malignant

Inflammation Matrix metalloproteinase Metastasis S100 protein Seed and soil hypothesis

Journal

Cancer letters

ISSN: 1872-7980

Titre abrégé: Cancer Lett

Pays: Ireland

ID NLM: 7600053

Informations de publication

Date de publication:
28 06 2019

Historique:

received: 17 11 2018

revised: 07 03 2019

accepted: 09 03 2019

pubmed: 25 3 2019

medline: 27 2 2020

entrez: 25 3 2019

Statut: ppublish

Résumé

Since metastasis accounts for the majority of cancer-associated deaths, studies on the mechanisms of metastasis are needed to establish innovative strategies for cancer treatment. We previously reported that melanoma cell adhesion molecule (MCAM) functions as a critical receptor for S100A8/A9, and binding of S100A8/A9 to MCAM results in the migration of melanoma cells to lung tissue. However, the critical role of MCAM in the original melanoma skin lesion is still not clear. In this study, we aimed to determine the importance of the S100A8/A9-MCAM axis in melanoma dissemination in a skin lesion as a critical early step for metastasis. Mechanistic studies revealed the downstream signaling of MCAM that signaled the induction of metastasis. S100A8/A9-MCAM binding activates mitogen-activated protein kinase kinase kinase 8 (MAP3K8), also termed TPL2, leading to strong activation of the transcription factor ETV4 and subsequent induction of matrix metalloproteinase-25 (MMP25), and finally to induction of melanoma lung tropic metastasis. Collectively, our results demonstrate a crucial role of the S100A8/A9-MCAM signaling axis in metastatic onset of melanoma cells and indicate that strategies targeting the identified pathway may be useful for the establishment of innovative anti-cancer therapies.

Identifiants

DOI: 10.1016/j.canlet.2019.03.023 PMID: 30904617

pubmed: 30904617

pii: S0304-3835(19)30179-X

doi: 10.1016/j.canlet.2019.03.023

pii:

doi:

Substances chimiques

CD146 Antigen 0

Calgranulin A 0

Calgranulin B 0

ETV4 protein, human 0

GPI-Linked Proteins 0

MCAM protein, human 0

Proto-Oncogene Proteins 0

Proto-Oncogene Proteins c-ets 0

RNA, Small Interfering 0

S100A8 protein, human 0

S100A9 protein, human 0

MAP Kinase Kinase Kinases EC 2.7.11.25

MAP3K8 protein, human EC 2.7.11.25

Matrix Metalloproteinases, Membrane-Associated EC 3.4.24.-

matrix metalloproteinase 25 EC 3.4.24.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

178-190