BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1 alpha activation

Li Andrew G.; Murphy Elizabeth C.; Culhane Aedin C.Powell EmilyWang HuaBronson Roderick T.Thanh VonGiobbie-Hurder AnitaGelman Rebecca S.Briggs Kimberly J.Piwnica-Worms HelenZhao Jean J.Kung Andrew L.Kaelin William G. Jr.Livingston David M.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1 alpha activation

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BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1 alpha activation

机译：BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1 alpha activation

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BRCA1 is an established breast and ovarian tumor suppressor gene that encodes multiple protein products whose individual contributions to human cancer suppression are poorly understood. BRCA1-IRIS (also known as "IRIS"), an alternatively spliced BRCA1 product and a chromatin-bound replication and transcription regulator, is overexpressed in various primary human cancers, including breast cancer, lung cancer, acute myeloid leukemia, and certain other carcinomas. Its naturally occurring overexpression can promote the metastasis of patient-derived xenograft (PDX) cells and other human cancer cells in mouse models. The IRIS-driven metastatic mechanism results from IRIS-dependent suppression of phosphatase and tensin homolog (PTEN) transcription, which in turn perturbs the PI3K/AKT/GSK-3 beta pathway leading to prolyl hydroxylase-independent HIF-1 alpha stabilization and activation in a normoxic environment. Thus, despite the tumor-suppressing genetic origin of IRIS, its properties more closely resemble those of an oncoprotein that, when spontaneously overexpressed, can, paradoxically, drive human tumor progression.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2018年第41期|E9600-E9609|共10页
作者
Li Andrew G.; Murphy Elizabeth C.; Culhane Aedin C.Powell EmilyWang HuaBronson Roderick T.Thanh VonGiobbie-Hurder AnitaGelman Rebecca S.Briggs Kimberly J.Piwnica-Worms HelenZhao Jean J.Kung Andrew L.Kaelin William G. Jr.Livingston David M.;
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作者单位

Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA;

Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USADana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USAUniv Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USAHarvard Med Sch, Dept Pathol, Boston, MA 02115 USADana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
BRCA1-IRIS; metastasis; HIF-1 alpha; PTEN;

BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1 alpha activation

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