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AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation
The mechanism of neuroendocrine transdifferentiation (NED) during the development of castration-resistant prostate cancer (CRPC) remains undefined. Although androgen-deprivation therapy (ADT) can impair tumor cell growth, ADT can also triggers a parallel reaction, leading to increased neurotensin (N...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842563/ http://dx.doi.org/10.21037/tau.2016.s007 |
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author | Zhu, Shimiao Shang, Zhiqun Tian, Hao Flores-Morales, Amilcar Niu, Yuanjie |
author_facet | Zhu, Shimiao Shang, Zhiqun Tian, Hao Flores-Morales, Amilcar Niu, Yuanjie |
author_sort | Zhu, Shimiao |
collection | PubMed |
description | The mechanism of neuroendocrine transdifferentiation (NED) during the development of castration-resistant prostate cancer (CRPC) remains undefined. Although androgen-deprivation therapy (ADT) can impair tumor cell growth, ADT can also triggers a parallel reaction, leading to increased neurotensin (NTS) production in cancer associated stromal cells which drives NED. Here, we systematically explore the NTS network in tumor microenvironment that drives NED following ADT. The CK8+/CK14+ intermediate cells, as opposed to other epithelial cells, can be transdifferentiated to neuroendocrine (NE) status by excessive NTS through simultaneous activation of neurotensin receptor 1 (NTSR1)-PRKACB and 3 (NTSR3)-AHNAK axes. The importance of PRKACB and AHNAK in NED development was then confirmed in human prostate tumor tissues. More importantly, we demonstrated SR48692 (an inhibitor of NTSR1) could inhibit NED and prevent castration resistance in prostate tumor from xenografts and TRAMP models. We propose that targeting this pathway could provide benefit for patients with tumors expressing high levels of NTS following ADT. |
format | Online Article Text |
id | pubmed-4842563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-48425632016-05-09 AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation Zhu, Shimiao Shang, Zhiqun Tian, Hao Flores-Morales, Amilcar Niu, Yuanjie Transl Androl Urol Plenary Session The mechanism of neuroendocrine transdifferentiation (NED) during the development of castration-resistant prostate cancer (CRPC) remains undefined. Although androgen-deprivation therapy (ADT) can impair tumor cell growth, ADT can also triggers a parallel reaction, leading to increased neurotensin (NTS) production in cancer associated stromal cells which drives NED. Here, we systematically explore the NTS network in tumor microenvironment that drives NED following ADT. The CK8+/CK14+ intermediate cells, as opposed to other epithelial cells, can be transdifferentiated to neuroendocrine (NE) status by excessive NTS through simultaneous activation of neurotensin receptor 1 (NTSR1)-PRKACB and 3 (NTSR3)-AHNAK axes. The importance of PRKACB and AHNAK in NED development was then confirmed in human prostate tumor tissues. More importantly, we demonstrated SR48692 (an inhibitor of NTSR1) could inhibit NED and prevent castration resistance in prostate tumor from xenografts and TRAMP models. We propose that targeting this pathway could provide benefit for patients with tumors expressing high levels of NTS following ADT. AME Publishing Company 2016-04 /pmc/articles/PMC4842563/ http://dx.doi.org/10.21037/tau.2016.s007 Text en 2016 Translational Andrology and Urology. All rights reserved. |
spellingShingle | Plenary Session Zhu, Shimiao Shang, Zhiqun Tian, Hao Flores-Morales, Amilcar Niu, Yuanjie AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation |
title | AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation |
title_full | AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation |
title_fullStr | AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation |
title_full_unstemmed | AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation |
title_short | AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation |
title_sort | ab007. neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation |
topic | Plenary Session |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842563/ http://dx.doi.org/10.21037/tau.2016.s007 |
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