Rho/ROCK Pathway Regulates Migration and Invasion of Esophageal Squamous Cell Carcinoma by Regulating Caveolin-1
Zhaohui Liu, Jing Yu, Ruinuan Wu, Shengxin Tang, Xiaoman Cai, Guanghua Guo, Suzuan Chen
Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China (mainland)
Med Sci Monit 2017; 23:6174-6185
Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. Caveolin-1 (Cav1) and Rho/ROCK pathway play important roles in tumor metastasis, separately. However, less research was focused on the relationship between Cav1 and Rho/ROCK in ECSS metastasis. Therefore, we investigated the relationship between Cav1 and Rho/ROCK pathway in ESCC metastasis.
MATERIAL AND METHODS: Cav1 and phosphorylated Cav1 (PY14Cav1) were examined in ESCC and in adjacent and non-tumorous tissues from ESCC patients by immunohistochemistry (IHC). Small interfering RNA (siRNA) targeting Cav1 or Rho/ROCK inhibitor was used to treat EC109, Eca109, TE1, and TE13 cells. Western blotting (WB) was used to detect Cav1 and PY14Cav1 expression. The wound healing scratch test and transwell assays were used to assess migration and invasion.
RESULTS: Cav1 and PY14Cav1 were gradually expressed at higher levels in ECSS than in adjacent and non-tumor tissues as ESCC stage and lymphatic metastasis increased, and this difference was significant (P<0.05). Cav1 was expressed at higher levels in TE1 and TE13 than in EC109 and Eca109, while PY14Cav1 was enhanced in TE1 and TE13 cells but not in EC109 and Eca109, and the difference was significant (P<0.05). TE1 and TE13 had significantly (P<0.05) stronger motility, migratory, and invasion abilities than EC109 and Eca109 cells. Silencing Cav1 decreased PY14Cav1 expression in TE1 and TE13 cells, as well as suppressing the migration and invasion of all ECSS cells, and these differences were significant (P<0.05). Suppressing the Rho/ROCK pathway obviously inhibited Cav1 and PY14Cav1 expressions, as well as significantly (P<0.05) decreasing migration and invasion of ESCC cells.
CONCLUSIONS: Cav1 and PY14Cav1 were positively correlated with ESCC lymphatic metastasis and cancer stages. Rho/ROCK pathway activation promoted ESCC metastasis by regulating Cav1.
Keywords: Caveolin 1, Cell Migration Assays, Neoplasm Invasiveness, Neoplasms, Squamous Cell, Signal Transduction