Journal Article
. 2009 Nov; 29(5):752-62.
doi: 10.1038/onc.2009.379.

Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed in vivo IFITM3 reduced OPN expression

M K El-Tanani 1 D Jin  F C Campbell  P G Johnston  
Affiliations
  • PMID: 19901966
  •     8 citations

Abstract

Osteopontin is a secreted, integrin-binding and phosphorylated acidic glycoprotein, which has an important role in tumour progression. We have shown that Wnt, Ets, AP-1, c-jun and beta-catenin/Lef-1/Tcf-1 stimulates OPN transcription in rat mammary carcinoma cells by binding to a specific promoter sequence. However, co-repressors of OPN have not been identified. In this study, we have used the bacterial two-hybrid system to isolate cDNA-encoding proteins that bind to OPN and modulate its role in malignant transformation. Using this approach we isolated interferon-induced transmembrane protein 3 gene (IFITM3) as a potential protein partner. We show that IFITM3 and OPN interact in vitro and in vivo and that IFITM3 reduces osteopontin (OPN) mRNA expression, possibly by affecting OPN mRNA stability. Stable transfection of IFITM3 inhibits OPN, which mediates anchorage-independent growth, cell adhesion and cell invasion. Northern blot analysis revealed an inverse mRNA expression pattern of IFITM3 and OPN in human mammary cell lines. Inhibition of IFITM3 by antisense RNA promoted OPN protein expression, enhanced cell invasion by parental benign non-invasive Rama 37 cells, indicating that the two proteins interact functionally as well. We also identified an IFITM3 DNA-binding domain, which interacts with OPN, deletion of which abolished its inhibitive effect on OPN. This work has shown for the first time that IFITM3 physically interacts with OPN and reduces OPN mRNA expression, which mediates cell adhesion, cell invasion, colony formation in soft agar and metastasis in a rat model system.

Expression of osteopontin coregulators in primary colorectal cancer and associated liver metastases.
D J Mole, C O'Neill, +6 authors, F C Campbell.
Br J Cancer, 2011 Feb 24; 104(6). PMID: 21343932    Free PMC article.
The role of IFITM3 in the growth and migration of human glioma cells.
Bing Zhao, Hongliang Wang, Gang Zong, Ping Li.
BMC Neurol, 2013 Dec 29; 13. PMID: 24370119    Free PMC article.
Role of osteopontin in the pathophysiology of cancer.
Lalita A Shevde, Rajeev S Samant.
Matrix Biol, 2014 Mar 25; 37. PMID: 24657887    Free PMC article.
Highly Cited. Review.
Overexpression of IFITM3 predicts the high risk of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy.
Yang Jia, Miao Zhang, +3 authors, Zhou Wang.
PeerJ, 2015 Nov 06; 3. PMID: 26539332    Free PMC article.
A Bayesian Approach for Analysis of Whole-Genome Bisulfite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation.
Owen J L Rackham, Sarah R Langley, +7 authors, Enrico Petretto.
Genetics, 2017 Feb 19; 205(4). PMID: 28213474    Free PMC article.
Interferon induced transmembrane protein 3 regulates the growth and invasion of human lung adenocarcinoma.
Dong Zhang, Huimin Wang, +2 authors, Yu Li.
Thorac Cancer, 2017 May 26; 8(4). PMID: 28544512    Free PMC article.
More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins.
Guoli Shi, Olivier Schwartz, Alex A Compton.
Retrovirology, 2017 Nov 23; 14(1). PMID: 29162141    Free PMC article.
Review.
Malignancy and IFITM3: Friend or Foe?
Ushani S Rajapaksa, Chen Jin, Tao Dong.
Front Oncol, 2020 Dec 29; 10. PMID: 33364194    Free PMC article.
Review.