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Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1.
Hsu, En-Chi; Rice, Meghan A; Bermudez, Abel; Marques, Fernando Jose Garcia; Aslan, Merve; Liu, Shiqin; Ghoochani, Ali; Zhang, Chiyuan Amy; Chen, Yun-Sheng; Zlitni, Aimen; Kumar, Sahil; Nolley, Rosalie; Habte, Frezghi; Shen, Michelle; Koul, Kashyap; Peehl, Donna M; Zoubeidi, Amina; Gambhir, Sanjiv S; Kunder, Christian A; Pitteri, Sharon J; Brooks, James D; Stoyanova, Tanya.
Afiliación
  • Hsu EC; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Rice MA; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Bermudez A; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Marques FJG; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Aslan M; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Liu S; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Ghoochani A; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Zhang CA; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Chen YS; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Zlitni A; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Kumar S; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Nolley R; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Habte F; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Shen M; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Koul K; Department of Urology, Stanford University, Stanford, CA 94304.
  • Peehl DM; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Zoubeidi A; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Gambhir SS; Department of Radiology, Stanford University, Stanford, CA 94304.
  • Kunder CA; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94304.
  • Pitteri SJ; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
  • Brooks JD; Department of Urology, Stanford University, Stanford, CA 94304.
  • Stoyanova T; Department of Radiology, Stanford University, Stanford, CA 94304.
Proc Natl Acad Sci U S A ; 117(4): 2032-2042, 2020 01 28.
Article en En | MEDLINE | ID: mdl-31932422
ABSTRACT
Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Óseas / Biomarcadores de Tumor / Moléculas de Adhesión Celular / Regulación Neoplásica de la Expresión Génica / Carcinoma Neuroendocrino / Neoplasias de la Próstata Resistentes a la Castración / Poli(ADP-Ribosa) Polimerasa-1 / Antígenos de Neoplasias Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Óseas / Biomarcadores de Tumor / Moléculas de Adhesión Celular / Regulación Neoplásica de la Expresión Génica / Carcinoma Neuroendocrino / Neoplasias de la Próstata Resistentes a la Castración / Poli(ADP-Ribosa) Polimerasa-1 / Antígenos de Neoplasias Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article