Verteporfin Inhibits Gastric Cancer Cell Growth by Suppressing Adhesion Molecule FAT1

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Dec 13

PMID 29228735

Citations 18

Authors

Myoung-Hee Kang

Gi Seok Jeong

Duane T Smoot

Hassan Ashktorab

Chang Mo Hwang

Byung Sik Kim

Hee Sung Kim

Yun-Yong Park

Affiliations

Soon will be listed here.

Abstract

Gastric cancer (GC) is a leading cause of death worldwide and in urgent need of targeted drug development. In the current, we investigated the ability of a repositioned drug verteporfin (VP), originally a treatment for macular degeneration, to inhibit GC cell growth. VP inhibited growth of various GC cell lines. Gene expression profiling of GC cell lines treated with VP revealed that migration-related genes and those with oncogenic potential were down-regulated. Of these genes, we found that FAT1, an adhesion molecule promoting cell invasion, was highly suppressed by VP. Silencing of FAT1 suppressed cell migration and invasion as VP did. FAT1 expression was up-regulated in tumors, and patients with high FAT1-expressing tumors had a worse prognosis. We propose that VP- targeting FAT1 to suppress metastatic potential is a promising therapeutic strategy against GC.

Citing Articles

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References

Zhao Y, Simon R . BRB-ArrayTools Data Archive for human cancer gene expression: a unique and efficient data sharing resource. Cancer Inform. 2009; 6:9-15. PMC: 2623314. DOI: 10.4137/cin.s448. View

Azab M, Benchaboune M, Blinder K, Bressler N, Bressler S, Gragoudas E . Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: Treatment Of Age-Related Macular Degeneration With Photodynamic Therapy.... Retina. 2004; 24(1):1-12. DOI: 10.1097/00006982-200402000-00001. View

Hartgrink H, Jansen E, van Grieken N, van de Velde C . Gastric cancer. Lancet. 2009; 374(9688):477-90. PMC: 4613761. DOI: 10.1016/S0140-6736(09)60617-6. View

van de Wetering M, Francies H, Francis J, Bounova G, Iorio F, Pronk A . Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015; 161(4):933-45. PMC: 6428276. DOI: 10.1016/j.cell.2015.03.053. View

Zhang H, Ramakrishnan S, Triner D, Centofanti B, Maitra D, Gyorffy B . Tumor-selective proteotoxicity of verteporfin inhibits colon cancer progression independently of YAP1. Sci Signal. 2015; 8(397):ra98. PMC: 4818013. DOI: 10.1126/scisignal.aac5418. View

Hu C, Ni Z, Li B, Yong X, Yang X, Zhang J . hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation. Gut. 2015; 66(1):31-42. DOI: 10.1136/gutjnl-2015-309322. View

Park J, Lee D, Lee E, Lee S . Study of cellular behaviors on concave and convex microstructures fabricated from elastic PDMS membranes. Lab Chip. 2009; 9(14):2043-9. DOI: 10.1039/b820955c. View

Park Y, Kim K, Kim S, Hennessy B, Kim S, Park E . Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO Mol Med. 2011; 4(1):52-67. PMC: 3376834. DOI: 10.1002/emmm.201100187. View

Alitalo K, Tammela T, Petrova T . Lymphangiogenesis in development and human disease. Nature. 2005; 438(7070):946-53. DOI: 10.1038/nature04480. View

10.

Liu-Chittenden Y, Huang B, Shim J, Chen Q, Lee S, Anders R . Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 2012; 26(12):1300-5. PMC: 3387657. DOI: 10.1101/gad.192856.112. View

11.

Ng C, Piscuoglio S, Geyer F, Burke K, Pareja F, Eberle C . The Landscape of Somatic Genetic Alterations in Metaplastic Breast Carcinomas. Clin Cancer Res. 2017; 23(14):3859-3870. PMC: 5511565. DOI: 10.1158/1078-0432.CCR-16-2857. View

12.

Long Z, Zhou M, Fu J, Chu X, Wang Y . Association between cadherin-17 expression and pathological characteristics of gastric cancer: a meta-analysis. World J Gastroenterol. 2015; 21(12):3694-705. PMC: 4375595. DOI: 10.3748/wjg.v21.i12.3694. View

13.

Hundahl S, Phillips J, Menck H . The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the "different disease" hypothesis. Cancer. 2000; 88(4):921-32. View

14.

Ye M, Du Y, Nie Y, Zhou Z, Cao J, Li Y . Overexpression of activated leukocute cell adhesion molecule in gastric cancer is associated with advanced stages and poor prognosis and miR-9 deregulation. Mol Med Rep. 2014; 11(3):2004-12. DOI: 10.3892/mmr.2014.2933. View

15.

Ciliberto D, Staropoli N, Caglioti F, Gualtieri S, Fiorillo L, Chiellino S . A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?. Cancer Biol Ther. 2015; 16(8):1148-59. PMC: 4623405. DOI: 10.1080/15384047.2015.1056415. View

16.

Pavelic K, Kolak T, Kapitanovic S, Radosevic S, Spaventi S, Kruslin B . Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its receptors (IGF 1R and M6-P/IGF 2R). J Pathol. 2003; 201(3):430-8. DOI: 10.1002/path.1465. View

17.

Scott L, Goa K . Verteporfin. Drugs Aging. 2000; 16(2):139-46; discussion 147-8. DOI: 10.2165/00002512-200016020-00005. View

18.

Wadhwa R, Song S, Lee J, Yao Y, Wei Q, Ajani J . Gastric cancer-molecular and clinical dimensions. Nat Rev Clin Oncol. 2013; 10(11):643-55. PMC: 3927982. DOI: 10.1038/nrclinonc.2013.170. View

19.

Karim S, Adelman R . Profile of verteporfin and its potential for the treatment of central serous chorioretinopathy. Clin Ophthalmol. 2013; 7:1867-75. PMC: 3788817. DOI: 10.2147/OPTH.S32177. View

20.

Chung S, Sudo R, Mack P, Wan C, Vickerman V, Kamm R . Cell migration into scaffolds under co-culture conditions in a microfluidic platform. Lab Chip. 2008; 9(2):269-75. DOI: 10.1039/b807585a. View