title: Filamin A interacting protein 1-like expression inhibits progression in colorectal cancer.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Young-Lan
authors.initials: YL
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Rul-Bin
authors.initials: RB
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Joong-Keun
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Sung-Yoon
authors.initials: SY
authors.lastname: Rew
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Myung
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Wan-Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Joo
mesh_terms: D000367:Age Factors; D000368:Aged; D043168:Angiostatins / Q000378:metabolism; D017209:Apoptosis; D063646:Carcinogenesis / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012737:Sex Factors; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C504459:FILIP1L protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; C579459:VEGFD protein, human; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D051176:beta Catenin; D043168:Angiostatins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: FILIP1L; angiogenesis; cell survival; colorectal neoplasm; prognosis