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Targeting ITGB4/SOX2-driven lung cancer stem cells using proteasome inhibitors.
Guo, Linlin; Mohanty, Atish; Singhal, Sharad; Srivastava, Saumya; Nam, Arin; Warden, Charles; Ramisetty, Sravani; Yuan, Yate-Ching; Cho, Hyejin; Wu, Xiwei; Li, Aimin; Vohra, Manik; Saladi, Srinivas Vinod; Wheeler, Deric; Arvanitis, Leonidas; Massarelli, Erminia; Kulkarni, Prakash; Zeng, Yiming; Salgia, Ravi.
Afiliação
  • Guo L; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Mohanty A; Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Respirology Medicine Centre of Fujian Province, Quanzhou, China.
  • Singhal S; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Srivastava S; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Nam A; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Warden C; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Ramisetty S; Integrative Genomics Core, Beckman Research Institute, City of Hope, Monrovia, CA 91016, USA.
  • Yuan YC; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Cho H; Divison of Translational Bioinformatics, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
  • Wu X; Integrative Genomics Core, Beckman Research Institute, City of Hope, Monrovia, CA 91016, USA.
  • Li A; Integrative Genomics Core, Beckman Research Institute, City of Hope, Monrovia, CA 91016, USA.
  • Vohra M; Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Saladi SV; Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
  • Wheeler D; Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
  • Arvanitis L; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Massarelli E; Department of Human Oncology, University of Wisconsin, Madison, WI, USA.
  • Kulkarni P; Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Zeng Y; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Salgia R; Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
iScience ; 26(8): 107302, 2023 Aug 18.
Article em En | MEDLINE | ID: mdl-37554452
ABSTRACT
This study investigates the role of integrin ß4 (ITGB4) and stemness-associated factor SOX2 in platinum resistance in lung squamous cell carcinoma (LUSC). The expression of SOX2 and ITGB4 is found to be high in all LUSC subtypes, but the impact of ITGB4 expression on overall patient survival varies by subtype. Cancer stem cells (CSCs) isolated from LUSC patients were found to be resistant to cisplatin, but knocking down ITGB4 or SOX2 sensitized them to cisplatin. Carfilzomib (CFZ) synergized with cisplatin and suppressed CSC growth by inhibiting ITGB4 and SOX2 expression. Additionally, CFZ was found to inhibit SOX2 expression epigenetically by inhibiting histone acetylation at the SOX2 promoter site. CFZ also suppressed the growth of SOX2-dependent small cell lung cancer cells in vitro and in vivo. The study highlights the unique function of CFZ as a transcriptional suppressor of SOX2, independent of its proteasome inhibitory function.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article