[PDF][PDF] PITPNC1 recruits RAB1B to the Golgi network to drive malignant secretion
Cancer cell, 2016•cell.com
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 …
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 …
Summary
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.
cell.com