TY - JOUR
T1 - Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration
AU - Wang, Yufeng
AU - Kuramitsu, Yasuhiro
AU - Kitagawa, Takao
AU - Baron, Byron
AU - Yoshino, Shigefumi
AU - Maehara, Shin Ichiro
AU - Maehara, Yoshihiko
AU - Oka, Masaaki
AU - Nakamura, Kazuyuki
N1 - Funding Information:
We thank Dr. Junko Akada and Dr. Kazuhiro Tokuda for discussion regarding this paper. We thank Dr. Nobuaki Suzuki and Dr. Tomio Ueno for providing us the pancreatic cancer tissues. This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (no. 24501352 to Yasuhiro Kuramitsu). Immunoblot detection by LAS-1000 was done at the Gene Research Centre of Yamaguchi University.
Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84924869310&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924869310&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2015.02.015
DO - 10.1016/j.canlet.2015.02.015
M3 - Article
C2 - 25684665
AN - SCOPUS:84924869310
SN - 0304-3835
VL - 360
SP - 171
EP - 176
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -
