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Expression of netrin-1 by hypoxia contributes to the invasion and migration of prostate carcinoma cells by regulating YAP activity.
Exp Cell Res. 2016 Dec 10; 349(2):302-309.EC

Abstract

Hypoxia is a hallmark of solid tumor growth microenvironment and appropriates the major contributor for the failure and poor prognosis of clinical tumor treatment, including prostate cancer (PCa). Ectopic expression of netrin-1 is reportedly associated with the progression of several carcinomas. Here, we aimed to investigate the role of netrin-1 in hypoxic metastasis potential of prostate carcinoma. Here, hypoxia induced the up-regulation of netrin-1 mRNA and protein expression in prostate cancer cell lines PC3 and DU145. Importantly, knockdown of netrin-1 dramatically suppressed cell invasion, migration and epithelial-to-mesenchymal transition (EMT) of PC3 and DU145 cells under hypoxia. Furthermore, hypoxia treatment increased the activity of Yes-associated protein (YAP) by increasing YAP expression in the nucleus and inhibiting p-YAP levels. However, YAP activation was notably restrained following netrin-1 down-regulation. Interestingly, interrupting YAP expression attenuated hypoxia-triggered cell invasion, migration and EMT of DU145 cells. More importantly, restoring YAP expression strikingly antagonized the inhibitory effects of netrin-1 decrease on the metastatic potential of prostate cancer cells. Together, these results indicate that netrin-1 may function as a positive regulator of hypoxia-triggered malignant behavior in PCa by activating the YAP signaling. Accordingly, netrin-1 could be a promising therapeutic agent against prostate carcinoma.

Authors+Show Affiliations

Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, PR China.Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, PR China. Electronic address: qichenqcf@sina.com.Department of Urology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, PR China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27815019

Citation

Chen, Haiwen, et al. "Expression of Netrin-1 By Hypoxia Contributes to the Invasion and Migration of Prostate Carcinoma Cells By Regulating YAP Activity." Experimental Cell Research, vol. 349, no. 2, 2016, pp. 302-309.
Chen H, Chen Q, Luo Q. Expression of netrin-1 by hypoxia contributes to the invasion and migration of prostate carcinoma cells by regulating YAP activity. Exp Cell Res. 2016;349(2):302-309.
Chen, H., Chen, Q., & Luo, Q. (2016). Expression of netrin-1 by hypoxia contributes to the invasion and migration of prostate carcinoma cells by regulating YAP activity. Experimental Cell Research, 349(2), 302-309. https://doi.org/10.1016/j.yexcr.2016.10.023
Chen H, Chen Q, Luo Q. Expression of Netrin-1 By Hypoxia Contributes to the Invasion and Migration of Prostate Carcinoma Cells By Regulating YAP Activity. Exp Cell Res. 2016 Dec 10;349(2):302-309. PubMed PMID: 27815019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of netrin-1 by hypoxia contributes to the invasion and migration of prostate carcinoma cells by regulating YAP activity. AU - Chen,Haiwen, AU - Chen,Qi, AU - Luo,Qidong, Y1 - 2016/11/01/ PY - 2016/06/28/received PY - 2016/10/17/revised PY - 2016/10/29/accepted PY - 2016/11/7/pubmed PY - 2017/5/17/medline PY - 2016/11/6/entrez KW - Cell invasion KW - Cell migration KW - Hypoxia KW - Netrin-1 KW - Prostate cancer KW - YAP SP - 302 EP - 309 JF - Experimental cell research JO - Exp. Cell Res. VL - 349 IS - 2 N2 - Hypoxia is a hallmark of solid tumor growth microenvironment and appropriates the major contributor for the failure and poor prognosis of clinical tumor treatment, including prostate cancer (PCa). Ectopic expression of netrin-1 is reportedly associated with the progression of several carcinomas. Here, we aimed to investigate the role of netrin-1 in hypoxic metastasis potential of prostate carcinoma. Here, hypoxia induced the up-regulation of netrin-1 mRNA and protein expression in prostate cancer cell lines PC3 and DU145. Importantly, knockdown of netrin-1 dramatically suppressed cell invasion, migration and epithelial-to-mesenchymal transition (EMT) of PC3 and DU145 cells under hypoxia. Furthermore, hypoxia treatment increased the activity of Yes-associated protein (YAP) by increasing YAP expression in the nucleus and inhibiting p-YAP levels. However, YAP activation was notably restrained following netrin-1 down-regulation. Interestingly, interrupting YAP expression attenuated hypoxia-triggered cell invasion, migration and EMT of DU145 cells. More importantly, restoring YAP expression strikingly antagonized the inhibitory effects of netrin-1 decrease on the metastatic potential of prostate cancer cells. Together, these results indicate that netrin-1 may function as a positive regulator of hypoxia-triggered malignant behavior in PCa by activating the YAP signaling. Accordingly, netrin-1 could be a promising therapeutic agent against prostate carcinoma. SN - 1090-2422 UR - https://www.unboundmedicine.com/medline/citation/27815019/Expression_of_netrin_1_by_hypoxia_contributes_to_the_invasion_and_migration_of_prostate_carcinoma_cells_by_regulating_YAP_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(16)30360-3 DB - PRIME DP - Unbound Medicine ER -