| Title | PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Halberg N, Sengelaub CA, Navrazhina K, Molina H, Uryu K, Tavazoie SF |
| Journal | Cancer Cell |
| Volume | 29 |
| Issue | 3 |
| Pagination | 339-353 |
| Date Published | 2016 Mar 14 |
| ISSN | 1878-3686 |
| Keywords | Animals, Breast Neoplasms, Cell Line, Cell Line, Tumor, Colonic Neoplasms, Female, Golgi Apparatus, Humans, Melanoma, Membrane Transport Proteins, Mice, Mice, Inbred BALB C, Mice, Inbred NOD, Mice, SCID, 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 |
| Alternate Journal | Cancer Cell |
| PubMed ID | 26977884 |
| PubMed Central ID | PMC5300038 |
| Grant List | T32 GM007739 / GM / NIGMS NIH HHS / United States T32GM007739 / GM / NIGMS NIH HHS / United States |
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