دورية أكاديمية
SMARCB1 regulates the hypoxic stress response in sickle cell trait.
| العنوان: | SMARCB1 regulates the hypoxic stress response in sickle cell trait. |
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| المؤلفون: | Soeung M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Perelli L; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Chen Z; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Dondossola E; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Ho IL; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Carbone F; Nerviano Medical Sciences, Milan 20014, Italy., Zhang L; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Khan H; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Le CN; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Zhu C; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Peoples MD; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Feng N; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Jiang S; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Zacharias NM; Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Minelli R; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Shapiro DD; Division of Urology, William S. Middleton Memorial VA Hospital, Madison, WI 53705., Deem AK; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Gao S; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Cheng EH; Department of Pathology, Memorial Sloan Kettering Cancer Institute, New York City, NY 10065., Lucchetti D; Department of Translational Medicine and Surgery-Faculty of Medicine and Surgery, Catholic University of the Sacred Heart, Rome 00168, Italy.; Multiplex Spatial Profiling Center, Fondazione Policlinico Universitario 'A. Gemelli', Rome 00168, Italy., Walker CL; Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030., Carugo A; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; Department of Oncology, IRBM S.p.A., Rome 00071, Italy., Giuliani V; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Heffernan TP; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Viale A; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Tannir NM; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Draetta GF; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Msaouel P; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030.; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025., Genovese G; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77025.; Translational Research to Advance Therapeutics and Innovation in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77025. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 May 23; Vol. 120 (21), pp. e2209639120. Date of Electronic Publication: 2023 May 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Carcinoma, Renal Cell*/pathology , Kidney Neoplasms*/pathology , Sickle Cell Trait*/genetics , Sickle Cell Trait*/metabolism, Animals ; Humans ; Mice ; Hypoxia/genetics ; Hypoxia/metabolism ; Kidney/metabolism ; SMARCB1 Protein/genetics ; SMARCB1 Protein/metabolism |
| مستخلص: | Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1 . Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies. |
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| معلومات مُعتمدة: | P30 CA008748 United States CA NCI NIH HHS; P50 CA140388 United States CA NCI NIH HHS; R01 CA223231 United States CA NCI NIH HHS; P30 CA016672 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: SMARCB1; hypoxia; renal medullary carcinoma; sickle cell trait |
| المشرفين على المادة: | 0 (SMARCB1 Protein) |
| تواريخ الأحداث: | Date Created: 20230515 Date Completed: 20230525 Latest Revision: 20240604 |
| رمز التحديث: | 20240604 |
| مُعرف محوري في PubMed: | PMC10214195 |
| DOI: | 10.1073/pnas.2209639120 |
| PMID: | 37186844 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.2209639120 |