Regulation of Breast Cancer Cell Motility by Golgi-Mediated Signaling

摘要

We have previously determined that the Rho-specific guanine nucleotide exchange factor, Dbs, regulates both normal and tumor cell motility. Since full-length Dbs localizes to the Golgi, we have determined whether Golgi- mediated signaling activities are required for breast cancer cell movement. Thus, stable MDA-MB-231 cell lines were established in which the activity of Golgi-localized Dbs was suppressed by a novel Sec14 domain-mediated genetic inhibitor. The level of endogenous activated Cdc42 was reduced in these cells suggesting that one function of Dbs is to regulate Golgi-localized Cdc42. Although the cells exhibited their normal mesenchymal morphology, they were impaired in their motility as measured by wound healing and transwell assays. Interestingly, the impairment was in directional migration, rather than cell movement per se. The cells were unable to reorient their Golgi in response to serum stimulation which likely accounts for the defect in directional movement.