Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration

Yufeng Wang, Yasuhiro Kuramitsu, Takao Kitagawa, Byron Baron, Shigefumi Yoshino, Shin Ichiro Maehara, Yoshihiko Maehara, Masaaki Oka, Kazuyuki Nakamura

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29 Citations (Scopus)

Abstract

Slingshot-1L (SSH1L), a cofilin-phosphatase, plays a role in actin dynamics and cell migration by reactivating cofilin-1. However, the expression of SSH1L in malignant diseases is poorly understood. The overexpression of SSH1L in cancerous tissue compared to the matched surrounding non-cancerous tissues from patients with late stages (III-IV) of PC was detected in 90% (9/10) of cases by western blotting. The expression of SSH1L was shown to be upregulated in tumor cells from 10.7% (11/102) of patients with pancreatic cancer (PC) by immunohistochemistry (IHC). The positive rate of SSH1L in patients with PC at stage VI (TNM) categorized as grade 3 was of 50% (2/4) and 15% (6/40), respectively. Moreover, SSH1L expression was shown to be up-regulated in the PC cell lines (KLM1, PANC-1 and MIAPaCa-2) with high metastatic potential. Loss of SSH1L expression was associated with an increase in the phosphorylation of cofilin-1 at serine-3 and further inhibited cell migration (but not proliferation) in KLM1, PANC-1 and MIAPaCa-2. Actin polymerization inhibitor cytochalasin-D was sufficient to abrogate cell migration of PC without changing SSH1L expression. These results reveal that SSH1L is upregulated in a subset of PCs and that the SSH1L/cofilin-1 signal pathway is associated positively in PC with cell migration. Our study may thus provide potential targets to prevent and/or treat PC invasion and metastasis in patients with SSH1L-positive PC.

Original languageEnglish
Pages (from-to)171-176
Number of pages6
JournalCancer Letters
Volume360
Issue number2
DOIs
Publication statusPublished - May 1 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Wang, Y., Kuramitsu, Y., Kitagawa, T., Baron, B., Yoshino, S., Maehara, S. I., Maehara, Y., Oka, M., & Nakamura, K. (2015). Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration. Cancer Letters, 360(2), 171-176. https://doi.org/10.1016/j.canlet.2015.02.015