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Article: Targeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma

TitleTargeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma
Authors
Issue Date10-Oct-2023
PublisherNational Academy of Sciences
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2023, v. 120, n. 42 How to Cite?
Abstract

Cancer-associated fibroblasts (CAFs) play vital roles in establishing a suitable tumor microenvironment. In this study, RNA sequencing data revealed that CAFs could promote cell proliferation, angiogenesis, and ECM reconstitution by binding to integrin families and activating PI3K/AKT pathways in esophageal squamous cell carcinoma (ESCC). The secretions of CAFs play an important role in regulating these biological activities. Among these secretions, we found that MFGE8 is specifically secreted by CAFs in ESCC. Additionally, the secreted MFGE8 protein is essential in CAF-regulated vascularization, tumor proliferation, drug resistance, and metastasis. By binding to Integrin αVβ3/αVβ5 receptors, MFGE8 promotes tumor progression by activating both the PI3K/AKT and ERK/AKT pathways. Interestingly, the biological function of MFGE8 secreted by CAFs fully demonstrated the major role of CAFs in ESCC and its mode of mechanism, showing that MFGE8 could be a driver factor of CAFs in remodeling the tumor environment. In vivo treatment targeting CAFs-secreting MFGE8 or its receptor produced significant inhibitory effects on ESCC growth and metastasis, which provides an approach for the treatment of ESCC.


Persistent Identifierhttp://hdl.handle.net/10722/338675
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737

 

DC FieldValueLanguage
dc.contributor.authorLiu, Beilei-
dc.contributor.authorZhang, Baifeng-
dc.contributor.authorQi, Jiali-
dc.contributor.authorZhou, Hongyu-
dc.contributor.authorTan, Licheng-
dc.contributor.authorHuang, Jinlin-
dc.contributor.authorHuang, Jiao-
dc.contributor.authorFang, Xiaona-
dc.contributor.authorGong, Lanqi-
dc.contributor.authorLuo, Jie-
dc.contributor.authorLiu, Shan-
dc.contributor.authorFu, Li-
dc.contributor.authorLing, Fei-
dc.contributor.authorMa, Stephianie-
dc.contributor.authorKwong, Dora Lai-wan-
dc.contributor.authorWang, Xin-
dc.contributor.authorGuan, Xin-Yuan-
dc.date.accessioned2024-03-11T10:30:41Z-
dc.date.available2024-03-11T10:30:41Z-
dc.date.issued2023-10-10-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2023, v. 120, n. 42-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/338675-
dc.description.abstract<p>Cancer-associated fibroblasts (CAFs) play vital roles in establishing a suitable tumor microenvironment. In this study, RNA sequencing data revealed that CAFs could promote cell proliferation, angiogenesis, and ECM reconstitution by binding to integrin families and activating PI3K/AKT pathways in esophageal squamous cell carcinoma (ESCC). The secretions of CAFs play an important role in regulating these biological activities. Among these secretions, we found that MFGE8 is specifically secreted by CAFs in ESCC. Additionally, the secreted MFGE8 protein is essential in CAF-regulated vascularization, tumor proliferation, drug resistance, and metastasis. By binding to Integrin αVβ3/αVβ5 receptors, MFGE8 promotes tumor progression by activating both the PI3K/AKT and ERK/AKT pathways. Interestingly, the biological function of MFGE8 secreted by CAFs fully demonstrated the major role of CAFs in ESCC and its mode of mechanism, showing that MFGE8 could be a driver factor of CAFs in remodeling the tumor environment. In vivo treatment targeting CAFs-secreting MFGE8 or its receptor produced significant inhibitory effects on ESCC growth and metastasis, which provides an approach for the treatment of ESCC.</p>-
dc.languageeng-
dc.publisherNational Academy of Sciences-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.titleTargeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma-
dc.typeArticle-
dc.identifier.doi10.1073/pnas.2307914120-
dc.identifier.volume120-
dc.identifier.issue42-
dc.identifier.eissn1091-6490-
dc.identifier.issnl0027-8424-

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