Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer

• Published in: Oncotarget 2016-11, Vol.7 (44), p.72229-72241
• Main Authors: Park, Young-Lan, Park, Sun-Young, Lee, Seung-Hyun, Kim, Rul-Bin, Kim, Joong-Keun, Rew, Sung-Yoon, Myung, Dae-Seong, Cho, Sung-Bum, Lee, Wan-Sik, Kim, Hyun-Soo, Joo, Young-Eun
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Angiostatins - metabolism; Apoptosis; beta Catenin - metabolism; Carcinogenesis - pathology; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Disease Progression; Female; Gene Knockdown Techniques; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta - metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Neoplasm Staging; Neovascularization, Pathologic - pathology; Phosphorylation; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; Research Paper; RNA Interference; RNA, Small Interfering - metabolism; Sex Factors; Tumor Burden; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor D - metabolism
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.12664

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.