Deletion of caveolin scaffolding domain alters cancer cell migration
| Autor: | Aayush Boddu, Yousuke T. Horikawa, Jonathan Okerblom, Sunaho Okada, Sadaf Azad Raja, Fiona Murray, Hideshi Okada, Itta Kawamura, Supriyo Ray, Yoshiteru Murofushi, Hemal H. Patel |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
STAT3 Transcription Factor Cell signaling Cellular differentiation Caveolin 1 Biology HeLa 03 medical and health sciences 0302 clinical medicine Protein Domains Cell Movement Neoplasms Caveolin Humans Neoplasm Metastasis Molecular Biology Cells Cultured Sequence Deletion Cell migration Cell Biology Cell cycle biology.organism_classification HCT116 Cells Cell biology G2 Phase Cell Cycle Checkpoints 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell cardiovascular system Signal transduction HT29 Cells Developmental Biology HeLa Cells Research Paper |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 |
| Popis: | Caveolin-1 (Cav-1) is an integral membrane protein that plays an important role in proliferative and terminally differentiated cells. As a structural component of Caveolae, Cav-1 interacts with signaling molecules via a caveolin scaffolding domain (CSD) regulating cell signaling. Recent reports have shown that Cav-1 is a negative regulator in tumor metastasis. Therefore, we hypothesize that Cav-1 inhibits cell migration through its CSD. HeLa cells were engineered to overexpress Cav-1 (Cav-1 OE), Cav-1 without a functional CSD (∆CSD), or enhanced green fluorescent protein (EGFP) as a control. HeLa cell migration was suppressed in Cav-1 OE cells while ∆CSD showed increased migration, which corresponded to a decrease in the tight junction protein, zonula occludens (ZO-1). The migration phenotype was confirmed in multiple cancer cell lines. Phosphorylated STAT-3 was decreased in Cav-1 OE cells compared to control and ∆CSD cells; reducing STAT-3 expression alone decreased cell migration. ∆CSD blunted HeLa proliferation by increasing the number of cells in the G2/M phase of the cell cycle. Overexpressing the CSD peptide alone suppressed HeLa cell migration and inhibited pSTAT3. These findings suggest that Cav-1 CSD may be critical in controlling the dynamic phenotype of cancer cells by facilitating the interaction of specific signal transduction pathways, regulating STAT3 and participating in a G2/M checkpoint. Modulating the CSD and targeting specific proteins may offer potential new therapies in the treatment of cancer metastasis. |
| Databáze: | OpenAIRE |
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