PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion.
| Publication Type | Academic Article |
| Authors | Halberg N, Sengelaub C, Navrazhina K, Molina H, Uryu K, Tavazoie S |
| Journal | Cancer Cell |
| Volume | 29 |
| Issue | 3 |
| Pagination | 339-353 |
| Date Published | 03/14/2016 |
| ISSN | 1878-3686 |
| Keywords | Golgi Apparatus, Membrane Transport Proteins, rab1 GTP-Binding Proteins |
| Abstract | Enhanced secretion of tumorigenic effector proteins is a feature of malignant cells. The molecular mechanisms underlying this feature are poorly defined. We identify PITPNC1 as a gene amplified in a large fraction of human breast cancer and overexpressed in metastatic breast, melanoma, and colon cancers. Biochemical, molecular, and cell-biological studies reveal that PITPNC1 promotes malignant secretion by binding Golgi-resident PI4P and localizing RAB1B to the Golgi. RAB1B localization to the Golgi allows for the recruitment of GOLPH3, which facilitates Golgi extension and enhanced vesicular release. PITPNC1-mediated vesicular release drives metastasis by increasing the secretion of pro-invasive and pro-angiogenic mediators HTRA1, MMP1, FAM3C, PDGFA, and ADAM10. We establish PITPNC1 as a PI4P-binding protein that enhances vesicular secretion capacity in malignancy. |
| DOI | 10.1016/j.ccell.2016.02.013 |
| PubMed ID | 26977884 |
| PubMed Central ID | PMC5300038 |