PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion

被引：114

作者：

Halberg, Nils ^{[1
,2
,3
]}

Sengelaub, Caitlin A. ^{[1
]}

Navrazhina, Kristina ^{[1
]}

Molina, Henrik ^{[1
]}

Uryu, Kunihiro ^{[1
]}

Tavazoie, Sohail F. ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Syst Canc Biol, Box 16,1230 York Ave, New York, NY 10065 USA

[2] Univ Bergen, Dept Biomed, Jonas Liesvej 91, N-5020 Bergen, Norway

[3] Univ Bergen, Dept Biomed, N-5020 Bergen, Norway

来源：

CANCER CELL | 2016年 / 29卷 / 03期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

PHOSPHATIDYLINOSITOL TRANSFER PROTEIN; BREAST-CANCER METASTASIS; STROMAL FIBROBLASTS; GENE-EXPRESSION; GOLPH3; OVEREXPRESSION; TRANSPORT; PHOSPHOINOSITIDES; MICRORNAS; INTERACTS;

D O I：

10.1016/j.ccell.2016.02.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：339 / 353

页数：15

共 42 条

[1] Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer [J].

Anan, K ;

Morisaki, T ;

Katano, M ;

Ikubo, A ;

Kitsuki, H ;

Uchiyama, A ;

Kuroki, S ;

Tanaka, M ;

Torisu, M .

SURGERY, 1996, 119 (03) :333-339

[2] PHOSPHOINOSITIDES: TINY LIPIDS WITH GIANT IMPACT ON CELL REGULATION [J].

Balla, Tamas .

PHYSIOLOGICAL REVIEWS, 2013, 93 (03) :1019-1137

[3] Rab GTPases and membrane identity: Causal or inconsequential? [J].

Barr, Francis A. .

JOURNAL OF CELL BIOLOGY, 2013, 202 (02) :191-199

[4] The landscape of somatic copy-number alteration across human cancers [J].

Beroukhim, Rameen ;

Mermel, Craig H. ;

Porter, Dale ;

Wei, Guo ;

Raychaudhuri, Soumya ;

Donovan, Jerry ;

Barretina, Jordi ;

Boehm, Jesse S. ;

Dobson, Jennifer ;

Urashima, Mitsuyoshi ;

Mc Henry, Kevin T. ;

Pinchback, Reid M. ;

Ligon, Azra H. ;

Cho, Yoon-Jae ;

Haery, Leila ;

Greulich, Heidi ;

Reich, Michael ;

Winckler, Wendy ;

Lawrence, Michael S. ;

Weir, Barbara A. ;

Tanaka, Kumiko E. ;

Chiang, Derek Y. ;

Bass, Adam J. ;

Loo, Alice ;

Hoffman, Carter ;

Prensner, John ;

Liefeld, Ted ;

Gao, Qing ;

Yecies, Derek ;

Signoretti, Sabina ;

Maher, Elizabeth ;

Kaye, Frederic J. ;

Sasaki, Hidefumi ;

Tepper, Joel E. ;

Fletcher, Jonathan A. ;

Tabernero, Josep ;

Baselga, Jose ;

Tsao, Ming-Sound ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Janne, Pasi A. ;

Daly, Mark J. ;

Nucera, Carmelo ;

Levine, Ross L. ;

Ebert, Benjamin L. ;

Gabriel, Stacey ;

Rustgi, Anil K. ;

Antonescu, Cristina R. ;

Ladanyi, Marc ;

Letai, Anthony .

NATURE, 2010, 463 (7283) :899-905

[5] CtBP3/BARS drives membrane fission in dynamin-independent transport pathways [J].

Bonazzi, M ;

Spanò, S ;

Turacchio, G ;

Cericola, C ;

Valente, C ;

Colanzi, A ;

Kweon, HS ;

Hsu, VW ;

Polishchuck, EV ;

Polishchuck, RS ;

Sallese, M ;

Pulvirenti, T ;

Corda, D ;

Luini, A .

NATURE CELL BIOLOGY, 2005, 7 (06) :570-U11

[6] Molecular Origins of Cancer Molecular Basis of Metastasis [J].

Chiang, Anne C. ;

Massague, Joan .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (26) :2814-2823

[7] GOLPH3 Bridges Phosphatidylinositol-4-Phosphate and Actomyosin to Stretch and Shape the Golgi to Promote Budding [J].

Dippold, Holly C. ;

Ng, Michelle M. ;

Farber-Katz, Suzette E. ;

Lee, Sun-Kyung ;

Kerr, Monica L. ;

Peterman, Marshall C. ;

Sim, Ronald ;

Wiharto, Patricia A. ;

Galbraith, Kenneth A. ;

Madhavarapu, Swetha ;

Fuchs, Greg J. ;

Meerloo, Timo ;

Farquhar, Marilyn G. ;

Zhou, Huilin ;

Field, Seth J. .

CELL, 2009, 139 (02) :337-351

[8] THE RAS-RELATED GTP-BINDING PROTEIN, RAB1B, REGULATES EARLY STEPS IN EXOCYTIC TRANSPORT AND PROCESSING OF BETA-AMYLOID PRECURSOR PROTEIN [J].

DUGAN, JM ;

DEWIT, C ;

MCCONLOGUE, L ;

MALTESE, WA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (18) :10982-10989

[9] Phosphatidylinositol Transfer Protein, Cytoplasmic 1 (PITPNC1) Binds and Transfers Phosphatidic Acid [J].

Garner, Kathryn ;

Hunt, Alan N. ;

Koster, Grielof ;

Somerharju, Pentti ;

Groves, Emily ;

Li, Michelle ;

Raghu, Padinjat ;

Holic, Roman ;

Cockcroft, Shamshad .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (38) :32263-32276

[10] The phosphatidylinositol transfer protein RdgBβ binds 14-3-3 via its unstructured C-terminus, whereas its lipid-binding domain interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein) [J].

Garner, Kathryn ;

Li, Michelle ;

Ugwuanya, Natalie ;

Cockcroft, Shamshad .

BIOCHEMICAL JOURNAL, 2011, 439 :97-111

← 1 2 3 4 5 →