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Updated: Mar 24, 2026

Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
Published on: January 26, 2015
PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion
Nils Halberg1, Caitlin A Sengelaub2, Kristina Navrazhina2
1Laboratory of Systems Cancer Biology, Rockefeller University, Box 16, 1230 York Avenue, New York, NY 10065, USA; Department of Biomedicine, University of Bergen, Jonas Liesvej 91, 5020 Bergen, Norway.
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.
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