Journal article
Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis
JCI insight, v 1(19), pp e86629-e86629
17 Nov 2016
PMID: 27882343
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing
mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of anoikis. We report here that estrogen increased LAM patient-derived cells' resistance to anoikis in vitro, accompanied by decreased accumulation of the proapoptotic protein Bim, an activator of anoikis. The resistance to anoikis was reversed by the proteasome inhibitor, bortezomib. Treatment of LAM patient-derived cells with estrogen plus bortezomib promoted anoikis compared with estrogen alone. Depletion of Bim by siRNA in TSC2-deficient cells resulted in anoikis resistance. Treatment of mice with bortezomib reduced estrogen-promoted lung colonization of TSC2-deficient cells. Importantly, molecular depletion of Bim by siRNA in Tsc2-deficient cells increased lung colonization in a mouse model. Collectively, these data indicate that Bim plays a key role in estrogen-enhanced survival of LAM patient-derived cells under detached conditions that occur with dissemination. Thus, targeting Bim may be a plausible future treatment strategy in patients with LAM.
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Details
- Title
- Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis
- Creators
- Chenggang Li - University of Cincinnati College of Medicine, Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Cincinnati, Ohio, USANa Li - The First Affiliated Hospital of Zhengzhou University, Department of Oncology, Zhengzhou, Henan, ChinaXiaolei Liu - University of Cincinnati College of Medicine, Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Cincinnati, Ohio, USAErik Y Zhang - University of Cincinnati College of Medicine, Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Cincinnati, Ohio, USAYang Sun - University of Cincinnati College of Medicine, Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Cincinnati, Ohio, USAKouhei Masuda - University of Cincinnati College of Medicine, Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Cincinnati, Ohio, USAJing Li - Harvard Medical School, Department of Cell Biology, Boston, Massachusetts, USAJulia Sun - University of Cincinnati College of Medicine, Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine, Cincinnati, Ohio, USATasha Morrison - Boston University School of Medicine, Department Molecular and Translational Medicine, Boston, Massachusetts, USAXiangke Li - The First Affiliated Hospital of Zhengzhou University, Department of Oncology, Zhengzhou, Henan, ChinaYuanguang Chen - The First Affiliated Hospital of Guangzhou Medical University, Department of Gastrointestinal Surgery, Guangzhou, ChinaJiang Wang - University of Cincinnati College of Medicine, Department of Pathology and Lab Medicine, Cincinnati, OH, USANagla A Karim - University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Hematology and Oncology, Cincinnati, Ohio, USAYi Zhang - The First Affiliated Hospital of Zhengzhou University, Biotherapy Center and Department of Oncology, Zhengzhou, Henan, ChinaJohn Blenis - Weill Cornell Medicine Sandra and Edward Meyer Cancer Center, New York, New York, USAMauricio J Reginato - Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania, USAElizabeth P Henske - Brigham and Women's Hospital-Harvard Medical School, Boston, Massachusetts, USAJane J Yu - The First Affiliated Hospital of Zhengzhou University, Department of Oncology, Zhengzhou, Henan, China
- Publication Details
- JCI insight, v 1(19), pp e86629-e86629
- Publisher
- American Society for Clinical Investigation; United States
- Grant note
- R01 HL098216 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000389797700001
- Scopus ID
- 2-s2.0-85055598462
- Other Identifier
- 991014877907504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental