Article ; Online: Ligand-independent integrin β1 signaling supports lung adenocarcinoma development.
JCI insight
2022 Volume 7, Issue 15
Abstract: Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted ... ...
| Abstract | Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that the highly expressed integrin β1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin β1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin β1-mediated adhesion to ECM but are dependent on integrin β1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). These studies support a critical role for integrin β1 in lung tumorigenesis that is mediated through constitutive, ECM binding-independent signaling involving the cytoplasmic tail. |
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| MeSH term(s) | Adenocarcinoma/genetics ; Adenocarcinoma of Lung/genetics ; Animals ; Humans ; Integrin beta1/genetics ; Integrin beta1/metabolism ; Integrins ; Ligands ; Lung Neoplasms/pathology ; Mice |
| Chemical Substances | Integrin beta1 ; Integrins ; Ligands |
| Language | English |
| Publishing date | 2022-08-08 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural |
| ISSN | 2379-3708 |
| ISSN (online) | 2379-3708 |
| DOI | 10.1172/jci.insight.154098 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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