title: Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration.
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.
authors: Departments of Biochemistry and Functional Proteomics, Digestive Surgery of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yufeng
authors: Y
authors: Wang
authors: Departments of Biochemistry and Functional Proteomics, Digestive Surgery of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: climates@yamaguchi-u.ac.jp.
authors: Yasuhiro
authors: Y
authors: Kuramitsu
authors: Departments of Biochemistry and Functional Proteomics, Digestive Surgery of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Takao
authors: T
authors: Kitagawa
authors: Departments of Biochemistry and Functional Proteomics, Digestive Surgery of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Byron
authors: B
authors: Baron
authors: Digestive Surgery of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Shigefumi
authors: S
authors: Yoshino
authors: Department of Surgery and Science, Graduate School of Medical Science, Kyusyu University, 3-1-1 Maidashi Higashiku, Fukuokashi, Fukuoka, Japan.
authors: Shin-Ichiro
authors: S
authors: Maehara
authors: Department of Surgery and Science, Graduate School of Medical Science, Kyusyu University, 3-1-1 Maidashi Higashiku, Fukuokashi, Fukuoka, Japan.
authors: Yoshihiko
authors: Y
authors: Maehara
authors: Digestive Surgery of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Masaaki
authors: M
authors: Oka
authors: Departments of Biochemistry and Functional Proteomics, Digestive Surgery of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine, Ube, Japan; Centre of Clinical Laboratories, Tokuyama Medical Association Hospital, Shunan, Japan.
authors: Kazuyuki
authors: K
authors: Nakamura
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000368:Aged; D002465:Cell Movement / Q000502:physiology; D051338:Cofilin 1 / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis*; D010766:Phosphorylation
chemical_list: D000199:Actins; D051338:Cofilin 1; D015638:Cytochalasin D; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human
keywords: Cell migration; Pancreatic cancer; SSH1L