PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion

Publication date: 14 March 2016
Source:Cancer Cell, Volume 29, Issue 3
Author(s): Nils Halberg, Caitlin A. Sengelaub, Kristina Navrazhina, Henrik Molina, Kunihiro Uryu, Sohail F. Tavazoie
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.

Teaser

Halberg et al. identify PITPNC1 as a gene amplified in a large fraction of human breast cancer and overexpressed in multiple cancer types. PITPNC1 drives malignancy and metastasis by binding Golgi-resident PI4P and localizing RAB1B to the Golgi, facilitating GOLPH3 recruitment and secretion of pro-tumor factors.


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