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Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer

Although docetaxel (DTX) confers significant survival benefits in patients with castration‐resistant prostate cancer (CRPC), resistance to DTX inevitably occurs. Therefore, clarifying the mechanisms of DTX resistance may improve survival in patients with CRPC. Claspin plays a pivotal role in DNA rep...

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Autores principales: Babasaki, Takashi, Sentani, Kazuhiro, Sekino, Yohei, Kobayashi, Go, Thang Pham, Quoc, Katsuya, Narutaka, Akabane, Shintaro, Taniyama, Daiki, Hayashi, Tetsutaro, Shiota, Masaki, Oue, Naohide, Teishima, Jun, Matsubara, Akio, Yasui, Wataru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366092/
https://www.ncbi.nlm.nih.gov/pubmed/34240817
http://dx.doi.org/10.1002/cam4.4113
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author Babasaki, Takashi
Sentani, Kazuhiro
Sekino, Yohei
Kobayashi, Go
Thang Pham, Quoc
Katsuya, Narutaka
Akabane, Shintaro
Taniyama, Daiki
Hayashi, Tetsutaro
Shiota, Masaki
Oue, Naohide
Teishima, Jun
Matsubara, Akio
Yasui, Wataru
author_facet Babasaki, Takashi
Sentani, Kazuhiro
Sekino, Yohei
Kobayashi, Go
Thang Pham, Quoc
Katsuya, Narutaka
Akabane, Shintaro
Taniyama, Daiki
Hayashi, Tetsutaro
Shiota, Masaki
Oue, Naohide
Teishima, Jun
Matsubara, Akio
Yasui, Wataru
author_sort Babasaki, Takashi
collection PubMed
description Although docetaxel (DTX) confers significant survival benefits in patients with castration‐resistant prostate cancer (CRPC), resistance to DTX inevitably occurs. Therefore, clarifying the mechanisms of DTX resistance may improve survival in patients with CRPC. Claspin plays a pivotal role in DNA replication stress and damage responses and is an essential regulator for the S‐phase checkpoint. CLSPN is an oncogenic gene that contributes to tumor proliferation in several human solid tumors. However, the clinical significance of claspin in prostate cancer (PCa) has not been examined. The present study aimed to elucidate the role of claspin and its relationship with DTX resistance in PCa. We immunohistochemically analyzed the expression of claspin in 89 PCa cases, of which 31 (35%) were positive for claspin. Claspin‐positive cases were associated with higher Gleason score, venous invasion, and perineural invasion. Kaplan–Meier analysis showed that high claspin expression was related to poor prostate‐specific antigen (PSA) relapse‐free prognosis. In a public database, high CLSPN expression was associated with poor PSA relapse‐free prognosis, Gleason score, T stage, lymph node metastasis, CRPC, and metastatic PCa. Claspin knockdown by siRNA decreased cell proliferation, upregulated DTX sensitivity, and suppressed the expression of Akt, Erk1/2, and CHK1 phosphorylation in DU145 and PC3 cell lines. Furthermore, claspin expression was much more upregulated in DTX‐resistant DU145 (DU145‐DR) than in parental DU145 cells. Claspin knockdown significantly upregulated the sensitivity to DTX in DU145‐DR cells. These results suggest that claspin plays an important role in PCa tumor progression and DTX resistance.
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spelling pubmed-83660922021-08-23 Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer Babasaki, Takashi Sentani, Kazuhiro Sekino, Yohei Kobayashi, Go Thang Pham, Quoc Katsuya, Narutaka Akabane, Shintaro Taniyama, Daiki Hayashi, Tetsutaro Shiota, Masaki Oue, Naohide Teishima, Jun Matsubara, Akio Yasui, Wataru Cancer Med Cancer Biology Although docetaxel (DTX) confers significant survival benefits in patients with castration‐resistant prostate cancer (CRPC), resistance to DTX inevitably occurs. Therefore, clarifying the mechanisms of DTX resistance may improve survival in patients with CRPC. Claspin plays a pivotal role in DNA replication stress and damage responses and is an essential regulator for the S‐phase checkpoint. CLSPN is an oncogenic gene that contributes to tumor proliferation in several human solid tumors. However, the clinical significance of claspin in prostate cancer (PCa) has not been examined. The present study aimed to elucidate the role of claspin and its relationship with DTX resistance in PCa. We immunohistochemically analyzed the expression of claspin in 89 PCa cases, of which 31 (35%) were positive for claspin. Claspin‐positive cases were associated with higher Gleason score, venous invasion, and perineural invasion. Kaplan–Meier analysis showed that high claspin expression was related to poor prostate‐specific antigen (PSA) relapse‐free prognosis. In a public database, high CLSPN expression was associated with poor PSA relapse‐free prognosis, Gleason score, T stage, lymph node metastasis, CRPC, and metastatic PCa. Claspin knockdown by siRNA decreased cell proliferation, upregulated DTX sensitivity, and suppressed the expression of Akt, Erk1/2, and CHK1 phosphorylation in DU145 and PC3 cell lines. Furthermore, claspin expression was much more upregulated in DTX‐resistant DU145 (DU145‐DR) than in parental DU145 cells. Claspin knockdown significantly upregulated the sensitivity to DTX in DU145‐DR cells. These results suggest that claspin plays an important role in PCa tumor progression and DTX resistance. John Wiley and Sons Inc. 2021-07-09 /pmc/articles/PMC8366092/ /pubmed/34240817 http://dx.doi.org/10.1002/cam4.4113 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Babasaki, Takashi
Sentani, Kazuhiro
Sekino, Yohei
Kobayashi, Go
Thang Pham, Quoc
Katsuya, Narutaka
Akabane, Shintaro
Taniyama, Daiki
Hayashi, Tetsutaro
Shiota, Masaki
Oue, Naohide
Teishima, Jun
Matsubara, Akio
Yasui, Wataru
Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer
title Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer
title_full Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer
title_fullStr Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer
title_full_unstemmed Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer
title_short Overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer
title_sort overexpression of claspin promotes docetaxel resistance and is associated with prostate‐specific antigen recurrence in prostate cancer
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366092/
https://www.ncbi.nlm.nih.gov/pubmed/34240817
http://dx.doi.org/10.1002/cam4.4113
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