Deletion of caveolin scaffolding domain alters cancer cell migration

Sunaho Okada, Sadaf A. Raja, Jonathan Okerblom, Aayush Boddu, Yousuke Horikawa, Supriyo Ray, Hideshi Okada, Itta Kawamura, Yoshiteru Murofushi, Fiona Murray, Hemal H. Patel (Corresponding Author)

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1268-1280
Number of pages13
JournalCell Cycle
Volume18
Issue number11
Early online date22 May 2019
DOIs
Publication statusPublished - 2019

Keywords

  • caveolin
  • cell migration

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    Okada, S., Raja, S. A., Okerblom, J., Boddu, A., Horikawa, Y., Ray, S., Okada, H., Kawamura, I., Murofushi, Y., Murray, F., & Patel, H. H. (2019). Deletion of caveolin scaffolding domain alters cancer cell migration. Cell Cycle, 18(11), 1268-1280. https://doi.org/10.1080/15384101.2019.1618118