Oncotarget

Research Papers:

DAPK and CIP2A are involved in GAS6/AXL-mediated Schwann cell proliferation in a rat model of bilateral cavernous nerve injury

Yen-Lin Chen, Yi-Ting Tsai, Ting-Ting Chao, Yi-No Wu, Meng-Chuan Chen, Ying-Hung Lin, Chun-Hou Liao, Shang-Shing P. Chou and Han-Sun Chiang _

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Oncotarget. 2018; 9:6402-6415. https://doi.org/10.18632/oncotarget.23978

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Abstract

Yen-Lin Chen1,2,3, Yi-Ting Tsai1, Ting-Ting Chao4, Yi-No Wu5, Meng-Chuan Chen6, Ying-Hung Lin3, Chun-Hou Liao3,7, Shang-Shing P. Chou2 and Han-Sun Chiang3,7

1Department of Pathology, Cardinal Tien Hospital, New Taipei, Taiwan

2Department of Chemistry, Fu-Jen Catholic University, New Taipei, Taiwan

3Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei, Taiwan

4Medical Research Center, Cardinal Tien Hospital, New Taipei, Taiwan

5School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan

6Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

7Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei, Taiwan

Correspondence to:

Han-Sun Chiang, email: [email protected]

Keywords: cavernous nerve; Schwann cell; CIP2A; DAPK; GAS6/AXL

Received: July 22, 2017    Accepted: October 28, 2017    Published: January 05, 2018

ABSTRACT

Purpose: Impotence is one of the major complications occurring in prostate cancer patients after radical prostectomy (RP). Self-repair of the injured nerve has been observed in animal models and in patients after RP. However, the downstream signalling is not well documented. Here, we found that the DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation.

Materials and Methods: The 3 groups were a sham group, a 14-day post-bilateral cavernous nerve injury (BCNI) group and a 28-day post-BCNI group. Erectile function was assessed and immunohistochemistry was performed. The rat Schwann cell RSC96 line was chosen for gene knockdown, cell viability, western blot, immunofluorescence and co-immunoprecipitation assays.

Results: The intracavernosal pressure was low on the 14th day after BCNI and partially increased by the 28th day. GAS6 and p-AXL expression gradually increased in the cavernous nerve after BCNI. RSC96 cells incubated with a GAS6 ligand showed increased levels of p-ERK1/2 and p-AKT. Moreover, DAPK and CIP2A.p-AXL and p-DAPK and CIP2A complexes were identified by both immunoblotting and co-immunoprecipitation.

Conclusion: The DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation. CIP2A inhibits PP2A activity, which results in p-DAPK(S308) maintenance and promotes Schwann cell proliferation. CIP2A is a potential target for the treatment of nerve injury after RP.


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