Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer
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Young-Lan Park1,*, Sun-Young Park1,*, Seung-Hyun Lee1, Rul-Bin Kim1, Joong-Keun Kim1, Sung-Yoon Rew1, Dae-Seong Myung1, Sung-Bum Cho1, Wan-Sik Lee1, Hyun-Soo Kim1, Young-Eun Joo1
1Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
*These authors contributed equally to this work
Young-Eun Joo, email: [email protected]
Keywords: FILIP1L, cell survival, angiogenesis, prognosis, colorectal neoplasm
Received: June 06, 2016 Accepted: October 10, 2016 Published: October 14, 2016
Filamin A interacting protein 1-like (FILIP1L) expression, which is decreased in various cancers, may inhibit carcinogenesis. In this study, we evaluated the effects of FILIP1L on oncogenic behavior and prognosis in colorectal cancer. siRNA-mediated FILIP1L knockdown enhanced tumor cell migration and invasion and inhibited apoptosis and cell cycle arrest in COLO205 cells. pcDNA-myc vector-mediated FILIP1L overexpression suppressed tumor cell migration and invasion and induced apoptosis and cell cycle arrest in HCT116 cells. FILIP1L knockdown enhanced angiogenesis by increasing VEGF-A and HIF-1α levels and decreasing angiostatin level. FILIP1L overexpression suppressed angiogenesis by decreasing VEGF-A and -D l level and increasing angiostatin and endostatin levels. Phosphorylated β-catenin levels decreased and phosphorylated Akt and GSK-3β levels increased following FILIP1L knockdown. FILIP1L overexpression had the opposite effects. FILIP1L expression was associated with reductions in tumor size, cell differentiation, lymphovascular invasion, stage, invasion depth and lymph node metastasis, and with longer overall survival. Mean Ki-67 labeling indexes and microvessel density values were lower in FILIP1L-positive tumors than in FILIP1L-negative tumors. These results indicate that FILIP1L suppresses tumor progression by inhibiting cell proliferation and angiogenesis in colorectal cancer.
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