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The NOGO receptor NgR2, a novel αVß3 integrin effector, induces neuroendocrine differentiation in prostate cancer.
Quaglia, Fabio; Krishn, Shiv Ram; Sossey-Alaoui, Khalid; Rana, Priyanka Shailendra; Pluskota, Elzbieta; Park, Pyung Hun; Shields, Christopher D; Lin, Stephen; McCue, Peter; Kossenkov, Andrew V; Wang, Yanqing; Goodrich, David W; Ku, Sheng-Yu; Beltran, Himisha; Kelly, William K; Corey, Eva; Klose, Maja; Bandtlow, Christine; Liu, Qin; Altieri, Dario C; Plow, Edward F; Languino, Lucia R.
Afiliación
  • Quaglia F; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.
  • Krishn SR; Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Sossey-Alaoui K; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.
  • Rana PS; Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Pluskota E; Department of Medicine, School of Medicine, MetroHealth Medical Center, Rammelkamp Center for Research, Case Western Reserve University, Cleveland, OH, USA.
  • Park PH; Department of Medicine, School of Medicine, MetroHealth Medical Center, Rammelkamp Center for Research, Case Western Reserve University, Cleveland, OH, USA.
  • Shields CD; Cardiovascular and Metabolic Sciences Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Lin S; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.
  • McCue P; Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Kossenkov AV; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.
  • Wang Y; Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Goodrich DW; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA.
  • Ku SY; Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Beltran H; Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Kelly WK; Center for Systems and Computational Biology, Wistar Institute, Philadelphia, PA, USA.
  • Corey E; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Klose M; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Bandtlow C; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Liu Q; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Altieri DC; Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Plow EF; Department of Urology, University of Washington, Seattle, WA, USA.
  • Languino LR; Institute of Neurochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Sci Rep ; 12(1): 18879, 2022 11 07.
Article en En | MEDLINE | ID: mdl-36344556
Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVß3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVß3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVß3, to which it associates; we also show that it promotes NED and anchorage-independent growth, as well as a motile phenotype of PrCa cells. Given our observations that high levels of αVß3 and, as shown here, of NgR2 are detected in human and mouse NEPrCa, our findings appear to be highly relevant to this aggressive and metastatic subtype of PrCa. This study is novel because NgR2 role has only minimally been investigated in cancer and has instead predominantly been analyzed in neurons. These data thus pave new avenues toward a comprehensive mechanistic understanding of integrin-directed signaling during PrCa progression toward a NE phenotype.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Carcinoma Neuroendocrino / Proteína NgR2 Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Carcinoma Neuroendocrino / Proteína NgR2 Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos