Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion.
Cell Rep
; 43(4): 114002, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38547126
ABSTRACT
The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.
Palavras-chave
CP: Cancer; EGF; EGFR; HGF; SCC; breast cancer; endocytosis; endosome; exosome; matriptase; protease
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Serina Endopeptidases
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Transdução de Sinais
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Invasividade Neoplásica
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China