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UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas.
Liu, Shiqin; Chai, Timothy; Garcia-Marques, Fernando; Yin, Qingqing; Hsu, En-Chi; Shen, Michelle; Shaw Toland, Angus Martin; Bermudez, Abel; Hartono, Alifiani B; Massey, Christopher F; Lee, Chung S; Zheng, Liwei; Baron, Maya; Denning, Caden J; Aslan, Merve; Nguyen, Holly M; Nolley, Rosalie; Zoubeidi, Amina; Das, Millie; Kunder, Christian A; Howitt, Brooke E; Soh, H Tom; Weissman, Irving L; Liss, Michael A; Chin, Arnold I; Brooks, James D; Corey, Eva; Pitteri, Sharon J; Huang, Jiaoti; Stoyanova, Tanya.
Afiliación
  • Liu S; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Chai T; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
  • Garcia-Marques F; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Yin Q; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Hsu EC; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Shen M; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Shaw Toland AM; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Bermudez A; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Hartono AB; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Massey CF; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Lee CS; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zheng L; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Baron M; Department of Pediatrics, Stanford University, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Denning CJ; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Aslan M; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Nguyen HM; Department of Urology, University of Washington, Seattle, WA, USA.
  • Nolley R; Department of Urology, Stanford University, Stanford, CA, USA.
  • Zoubeidi A; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
  • Das M; Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA, USA; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, USA.
  • Kunder CA; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Howitt BE; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Soh HT; Department of Radiology, Stanford University, Palo Alto, CA, USA; Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
  • Weissman IL; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA, USA.
  • Liss MA; Department of Urology, UT Health San Antonio, San Antonio, TX, USA.
  • Chin AI; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Brooks JD; Department of Urology, Stanford University, Stanford, CA, USA.
  • Corey E; Department of Urology, University of Washington, Seattle, WA, USA.
  • Pitteri SJ; Department of Radiology, Stanford University, Palo Alto, CA, USA.
  • Huang J; Department of Pathology, Duke University, Durham, NC, USA.
  • Stoyanova T; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiology, Stanford University, Palo Alto, CA, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: tstoyanova@mednet.u
Cell Rep Med ; 5(2): 101381, 2024 Feb 20.
Article en En | MEDLINE | ID: mdl-38244540
ABSTRACT
Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of UCHL1 inhibitors with cisplatin, the standard of care used for neuroendocrine carcinomas, significantly delays tumor growth in pre-clinical settings. Our study reveals mechanisms of UCHL1 function in regulating the progression of neuroendocrine carcinomas and identifies UCHL1 as a therapeutic target and potential molecular indicator for diagnosing and monitoring treatment responses in these malignancies.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma Neuroendocrino / Carcinoma Pulmonar de Células Pequeñas / Neoplasias Pulmonares Límite: Humans / Male Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma Neuroendocrino / Carcinoma Pulmonar de Células Pequeñas / Neoplasias Pulmonares Límite: Humans / Male Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos