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Targeting prostate tumor low-molecular weight tyrosine phosphatase for oxidation-sensitizing therapy.
Stanford, Stephanie M; Nguyen, Tiffany P; Chang, Joseph; Zhao, Zixuan; Hackman, G Lavender; Santelli, Eugenio; Sanders, Colton M; Katiki, Madhusudhanarao; Dondossola, Eleonora; Brauer, Brooke L; Diaz, Michael A; Zhan, Yuan; Ramsey, Sterling H; Watson, Philip A; Sankaran, Banumathi; Paindelli, Claudia; Parietti, Vanessa; Mikos, Antonios G; Lodi, Alessia; Bagrodia, Aditya; Elliott, Andrew; McKay, Rana R; Murali, Ramachandran; Tiziani, Stefano; Kettenbach, Arminja N; Bottini, Nunzio.
Afiliación
  • Stanford SM; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Nguyen TP; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Chang J; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Zhao Z; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Hackman GL; Department of Nutritional Sciences, College of Natural Sciences and Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
  • Santelli E; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Sanders CM; Kao Autoimmunity Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Katiki M; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Dondossola E; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Brauer BL; Department of Genitourinary Medical Oncology and David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Diaz MA; Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
  • Zhan Y; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
  • Ramsey SH; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Watson PA; Department of Pediatrics and Department of Oncology, Dell Medical School, Livestrong Cancer Institutes, College of Natural Sciences, The University of Texas at Austin, Austin, TX USA.
  • Sankaran B; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Paindelli C; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Parietti V; Department of Molecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
  • Mikos AG; Department of Genitourinary Medical Oncology and David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lodi A; Department of Genitourinary Medical Oncology and David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Bagrodia A; Department of Bioengineering, Rice University, Houston, TX, USA.
  • Elliott A; Department of Nutritional Sciences, College of Natural Sciences and Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
  • McKay RR; Department of Urology, University of California, San Diego, La Jolla, CA, USA.
  • Murali R; Department of Clinical and Translational Research, Caris Life Sciences, Phoenix, AZ, USA.
  • Tiziani S; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Kettenbach AN; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Bottini N; Department of Nutritional Sciences, College of Natural Sciences and Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Sci Adv ; 10(5): eadg7887, 2024 Feb 02.
Article en En | MEDLINE | ID: mdl-38295166
ABSTRACT
Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor 2-mediated stress response, and enhanced reactive oxygen species after exposure to taxane drugs. LMPTP inhibition slowed primary and bone metastatic prostate tumor growth in mice. These findings reveal a role for LMPTP as a critical promoter of PCa growth and metastasis and validate LMPTP inhibition as a therapeutic strategy for treating PCa through sensitization to oxidative stress.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos