Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion
Summary: 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-m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724003309 |
| _version_ | 1797238074402406400 |
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| author | Fang Ye Zhikang Yuan Ying Tang Jiamei Li Xingxing Liu Xuedi Sun Shuang Chen Xiaohong Ye Zhiping Zeng Xiao-kun Zhang Hu Zhou |
| author_facet | Fang Ye Zhikang Yuan Ying Tang Jiamei Li Xingxing Liu Xuedi Sun Shuang Chen Xiaohong Ye Zhiping Zeng Xiao-kun Zhang Hu Zhou |
| author_sort | Fang Ye |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-24T17:29:52Z |
| format | Article |
| id | doaj.art-dffc264fa74245d9a284dd171b817cf5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T17:29:52Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-dffc264fa74245d9a284dd171b817cf52024-03-28T06:37:45ZengElsevierCell Reports2211-12472024-04-01434114002Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasionFang Ye0Zhikang Yuan1Ying Tang2Jiamei Li3Xingxing Liu4Xuedi Sun5Shuang Chen6Xiaohong Ye7Zhiping Zeng8Xiao-kun Zhang9Hu Zhou10School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian 361102, ChinaSchool of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian 361102, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724003309CP: Cancer |
| spellingShingle | Fang Ye Zhikang Yuan Ying Tang Jiamei Li Xingxing Liu Xuedi Sun Shuang Chen Xiaohong Ye Zhiping Zeng Xiao-kun Zhang Hu Zhou Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion Cell Reports CP: Cancer |
| title | Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion |
| title_full | Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion |
| title_fullStr | Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion |
| title_full_unstemmed | Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion |
| title_short | Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion |
| title_sort | endocytic activation and exosomal secretion of matriptase stimulate the second wave of egf signaling to promote skin and breast cancer invasion |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724003309 |
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