Ligand-independent integrin beta1 signaling supports lung adenocarcinoma development
dc.contributor.advisor | Zent, Roy | |
dc.creator | Haake, Scott Mattox | |
dc.date.accessioned | 2022-09-21T17:49:25Z | |
dc.date.available | 2022-09-21T17:49:25Z | |
dc.date.created | 2022-08 | |
dc.date.issued | 2022-07-13 | |
dc.date.submitted | August 2022 | |
dc.identifier.uri | http://hdl.handle.net/1803/17786 | |
dc.description.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 beta1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin beta1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin beta1-mediated adhesion to ECM but are dependent on integrin beta1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). Together, these studies support a critical role for integrin beta1 in lung tumorigenesis that is mediated through constitutive, ECM-binding independent signaling involving the cytoplasmic tail. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.subject | integrin | |
dc.subject | integrin beta1 | |
dc.subject | cytoplasmic tail | |
dc.subject | FAK | |
dc.subject | cancer | |
dc.subject | cell proliferation | |
dc.subject | gene transcription | |
dc.subject | extracellular matrix | |
dc.title | Ligand-independent integrin beta1 signaling supports lung adenocarcinoma development | |
dc.type | Thesis | |
dc.date.updated | 2022-09-21T17:49:25Z | |
dc.type.material | text | |
thesis.degree.name | PhD | |
thesis.degree.level | Doctoral | |
thesis.degree.discipline | Cancer Biology | |
thesis.degree.grantor | Vanderbilt University Graduate School | |
dc.creator.orcid | 0000-0003-3455-0791 | |
dc.contributor.committeeChair | Pozzi, Ambra |
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