Erratum for the Research Article: 'PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma' by X. Tan, P. Banerjee, E. A. Pham, F. U. N. Rutaganira, K. Basu, N. Bota-Rabassedas, H.-F. Guo, C. L. Grzeskowiak, X. Liu, J. Yu, L. Shi, D. H. Peng, B. L. Rodriguez, J. Zhang, V. Zheng, D. Y. Duose, L. M. Solis, B. Mino, M. G. Raso, C. Behrens, I. I. Wistuba, K. L. Scott, M. Smith, K. Nguyen, G. Lam, I. Choong, A. Mazumdar, J. L. Hill, D. L. Gibbons, P. H. Brown, W. K. Russell, K. Shokat, C. J. Creighton, J. S. Glenn, J. M. Kurie
| Autor: | Ignacio I. Wistuba, Priyam Banerjee, B. L. Rodriguez, Mark Smith, Caitlin L. Grzeskowiak, Veronica J. Zheng, Dzifa Y. Duose, David H. Peng, Xiaochao Tan, Powel H. Brown, Chad J. Creighton, Jiang Yu, Luisa M. Solis, Khanh Nguyen, Carmen Behrens, Maria Gabriela Raso, Kevan M. Shokat, Lei Shi, Barbara Mino, Hou Fu Guo, Jamal Hill, Jonathan M. Kurie, Florentine U. Rutaganira, Ingrid Choong, Don L. Gibbons, Neus Bota-Rabassedas, Basu Kaustabh, Jeffrey S. Glenn, Jianhua Zhang, William K. Russell, Abhijit Mazumdar, G. Lam, Xi Liu, Kenneth L. Scott |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Sci Transl Med |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.abb5995 |
| Popis: | Heightened secretion of pro-tumorigenic effector proteins is a feature of malignant cells. Yet the molecular underpinnings and therapeutic implications of this feature remain unclear. Here we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell-biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)-dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence pro-metastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression. |
| Databáze: | OpenAIRE |
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