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Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor

MPHOSPH1, which is one of the kinesin superfamily proteins, has been reported to play an essential role in the carcinogenesis and progression of several kinds of cancers. MPHOSPH1 has also been suggested to be involved in STAT3 phosphorylation in hepatocellular carcinoma. However, the biological beh...

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Autores principales: Abe, Tatsuro, Kohashi, Kenichi, Takemoto, Junkichi, Kinoshita, Fumio, Eto, Masatoshi, Oda, Yoshinao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277652/
https://www.ncbi.nlm.nih.gov/pubmed/30519350
http://dx.doi.org/10.7150/jca.25279
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author Abe, Tatsuro
Kohashi, Kenichi
Takemoto, Junkichi
Kinoshita, Fumio
Eto, Masatoshi
Oda, Yoshinao
author_facet Abe, Tatsuro
Kohashi, Kenichi
Takemoto, Junkichi
Kinoshita, Fumio
Eto, Masatoshi
Oda, Yoshinao
author_sort Abe, Tatsuro
collection PubMed
description MPHOSPH1, which is one of the kinesin superfamily proteins, has been reported to play an essential role in the carcinogenesis and progression of several kinds of cancers. MPHOSPH1 has also been suggested to be involved in STAT3 phosphorylation in hepatocellular carcinoma. However, the biological behavior of MPHOSPH1 in testicular germ cell tumors (TGCTs) is unclear at present. The purposes of this study were to investigate the correlation between the expression of MPHOSPH1 and clinicopathological factors and to examine the efficacy of MPHOSPH1 target therapy in TGCTs. We investigated 75 formalin-fixed paraffin-embedded TGCT samples, containing a total of 86 germ cell tumor components, by immunohistochemistry and 12 frozen samples by Western blotting. Moreover, we carried out in vitro studies to clarify the antitumor effect of MPHOSPH1 knockdown in embryonal carcinoma cell lines, NEC8 and NEC14, using small interference RNA (siRNA). A significantly high expression of MPHOSPH1 was recognized in embryonal carcinoma and yolk sac tumor components compared to the seminoma component (p<0.001, respectively). Clinically, non-seminoma cases are known to have worse prognosis than pure-seminoma cases. Interestingly, high MPHOSPH1 expression was associated with distant metastasis (p=0.001), and thus with advanced-stage disease in this study. High expression of MPHOSPH1 interacted with high expression of phosphorylated STAT3 (p=0.01). The in vitro experiments demonstrated that MPHOSPH1 interruption by siRNA resulted in a significant reduction of cell migration, invasion, proliferation and colony formation in both embryonal carcinoma cell lines (p<0.001, respectively). In conclusion, MPHOSPH1 may be a potential treatment option for TGCTs, and its expression may be a novel biomarker of poor prognosis.
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spelling pubmed-62776522018-12-05 Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor Abe, Tatsuro Kohashi, Kenichi Takemoto, Junkichi Kinoshita, Fumio Eto, Masatoshi Oda, Yoshinao J Cancer Research Paper MPHOSPH1, which is one of the kinesin superfamily proteins, has been reported to play an essential role in the carcinogenesis and progression of several kinds of cancers. MPHOSPH1 has also been suggested to be involved in STAT3 phosphorylation in hepatocellular carcinoma. However, the biological behavior of MPHOSPH1 in testicular germ cell tumors (TGCTs) is unclear at present. The purposes of this study were to investigate the correlation between the expression of MPHOSPH1 and clinicopathological factors and to examine the efficacy of MPHOSPH1 target therapy in TGCTs. We investigated 75 formalin-fixed paraffin-embedded TGCT samples, containing a total of 86 germ cell tumor components, by immunohistochemistry and 12 frozen samples by Western blotting. Moreover, we carried out in vitro studies to clarify the antitumor effect of MPHOSPH1 knockdown in embryonal carcinoma cell lines, NEC8 and NEC14, using small interference RNA (siRNA). A significantly high expression of MPHOSPH1 was recognized in embryonal carcinoma and yolk sac tumor components compared to the seminoma component (p<0.001, respectively). Clinically, non-seminoma cases are known to have worse prognosis than pure-seminoma cases. Interestingly, high MPHOSPH1 expression was associated with distant metastasis (p=0.001), and thus with advanced-stage disease in this study. High expression of MPHOSPH1 interacted with high expression of phosphorylated STAT3 (p=0.01). The in vitro experiments demonstrated that MPHOSPH1 interruption by siRNA resulted in a significant reduction of cell migration, invasion, proliferation and colony formation in both embryonal carcinoma cell lines (p<0.001, respectively). In conclusion, MPHOSPH1 may be a potential treatment option for TGCTs, and its expression may be a novel biomarker of poor prognosis. Ivyspring International Publisher 2018-10-31 /pmc/articles/PMC6277652/ /pubmed/30519350 http://dx.doi.org/10.7150/jca.25279 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Abe, Tatsuro
Kohashi, Kenichi
Takemoto, Junkichi
Kinoshita, Fumio
Eto, Masatoshi
Oda, Yoshinao
Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor
title Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor
title_full Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor
title_fullStr Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor
title_full_unstemmed Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor
title_short Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor
title_sort clinicopathological significance and antitumor effect of mphosph1 in testicular germ cell tumor
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277652/
https://www.ncbi.nlm.nih.gov/pubmed/30519350
http://dx.doi.org/10.7150/jca.25279
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