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PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion.

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.

SUBMITTER: Halberg N

PROVIDER: S-EPMC5300038 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion.

Halberg Nils N Sengelaub Caitlin A CA Navrazhina Kristina K Molina Henrik H Uryu Kunihiro K Tavazoie Sohail F SF

Cancer cell 20160301 3

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 G ...[more]

PMID: 26977884

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