RT Journal Article
SR Electronic
T1 Gelsolin Governs the Neuroendocrine Transdifferentiation of Prostate Cancer Cells and Suppresses the Apoptotic Machinery
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3717
OP 3729
DO 10.21873/anticanres.15163
VO 41
IS 8
A1 FELIX OELRICH
A1 HEIKE JUNKER
A1 MATTHIAS B. STOPE
A1 HOLGER H.H. ERB
A1 REINHARD WALTHER
A1 SIMONE VENZ
A1 UWE ZIMMERMANN
YR 2021
UL http://ar.iiarjournals.org/content/41/8/3717.abstract
AB Background/Aim: Interleukin 6 (IL6) is increased in patients with progressive prostate cancer and induces its transdifferentiation to neuroendocrine prostate cancer. Neuroendocrine prostate cancer has become one of the greatest challenges in treating castration-resistant disease and is linked to poor prognosis. It is necessary to understand better the cellular events associated with IL6-mediated neuroendocrine differentiation to prevent it and identify potential new therapeutic targets. Materials and Methods: In the present study, an IL6-inducible neuroendocrine differentiation model established specifically for this purpose was applied using LNCaP cells. Proteomics and western blot analyses were used to identify proteins involved in neuroendocrine differentiation. Subsequently, the role of gelsolin (GSN) in the neuroendocrine differentiation model was characterized (knock-down analyses, microscopic co-localization analyses, apoptosis assay) and GSN expression levels in patient material were investigated. Results: This study revealed that GSN is a crucial factor in the neuroendocrine differentiation process. Conclusion: It was shown that siRNA-mediated knock-down of GSN can inhibit neuroendocrine differentiation, making it a valid target for preventing IL6-mediated neuroendocrine differentiation.