Document Type
Article
Publication Date
11-7-2022
Abstract
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 αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 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 αVβ3, 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 αVβ3 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.
Recommended Citation
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.; and Languino, Lucia R., "The NOGO Receptor NgR2, A Novel αVβ3 Integrin Effector, Induces Neuroendocrine Differentiation in Prostate Cancer" (2022). Department of Cancer Biology Faculty Papers. Paper 196.
https://jdc.jefferson.edu/cbfp/196
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
36344556
Language
English
Comments
This is the author's final published version in Scientific Reports, Volume 12, Issue 1, December 2022, Article number 18879.
The published version is available at https://doi.org/10.1038/s41598-022-21711-5. Copyright © The Author(s) 2022.