Caveolin scaffolding domain plays an important role in cancer cell migration

Abstract

Caveolin‐1 is the integral membrane protein that plays an important role in the structure and function of terminally differentiated cells. As a structural component of caveolae, the caveolin scaffolding domain (CSD) has been associated with many cellular signaling processes and recent reports have implicated Cav‐1 as a negative regulator in tumor metastasis. We hypothesized that Cav‐1 may be inhibiting cell migration through its CSD. To assess this, HCT‐116 cells (which contain high endogenous Cav1) and HT‐29 cells (which contain low endogenous Cav1) were transduced with a lentiviral construct expressing either Cav‐1 or Cav‐1 without a functional CSD (ΔCSD). HeLa cells were also genetically engineered to stably overexpress Cav‐1(Cav‐1 OE), ΔCSD, or enhanced green fluorescent protein (EGFP) as a comparative control. In all cases, migration was significantly greater in ΔCSD cells compared to Cav‐1 OE and control cells. Phosphorylated STAT‐3 was also decreased in Cav‐1 OE cells compared to control and ΔCSD cells. G2/M phase was significantly increased and G1 was decreased in ΔCSD cells compared to control and CAV1 OE cells. Cdc2 phosphorylation was also increased in ΔCSD cells. To further confirm that CSD affects cell migration, we performed migration assays in Hela cells expressing either a pEGFP tagged CSD or a scrambled sequence. CSD overexpressing cells showed a lower migration rate comparison to control cells. These findings suggest that Cav‐1 CSD affects cell migration, possibly by participating in a G2/M checkpoint. These findings may represent a new approach to the treatment of cancer metastasis.Support or Funding InformationNIH R01 HL091071This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.