Fra-1 Governs Cell Migration Via Modulation of CD44 Expression in Human Mesotheliomas

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2007 Dec 22

PMID 18096084

Citations 15

Authors

Maria E Ramos-Nino

Steven R Blumen

Harvey Pass

Brooke T Mossman

Affiliations

Soon will be listed here.

Abstract

Silencing of Fra-1, a component of the dimeric transcription factor, activator protein-1 (AP-1), inhibits mRNA expression of c-met and cd44 in rat mesothelioma cells and is causally linked to maintenance of the transformed phenotype. However, the mechanisms of Fra-1 regulation and Fra-1 regulated gene expression in human malignant mesothelioma (MM) are unclear. We first show in a panel of human MM cells that Fra-1 mRNA expression in MM is complex and regulated by extracellular signal-regulated kinase (ERK1, ERK2), Src, and phosphatidyl-inositol-3-kinase (PI3K) pathways in a tumor-specific fashion. Cell lines with PI3K-dependent Fra-1 expression were SV40 positive and expressed the lowest basal Fra-1 levels. Levels of Fra-1 expression correlated with amounts of CD44 expression that were greater in simian virus 40 negative (SV40-) MM cells. Using dominant negative (dn), short hairpin (sh) and small interference (si) RNA constructs, we next demonstrate that expression of CD44, the principal hyaluronic receptor in MMs, correlates with Fra-expression in both simian virus 40 positive (SV40+) and SV40- MMs. Moreover, both Fra-1 and CD44 expression are linked to cell migration in SV40- MM cells. Lastly, in contrast to normal lung tissue, tissue microarrays revealed that Fra-1 was expressed in 33 of 34 human MMs, and that all CD44+ tumors were SV40-. These results suggest that Fra-1 is associated with cell migration in human MMs and that Fra-1 modulation of CD44 may govern migration of selected MMs.

Citing Articles

Construction of multifunctional hydrogel with metal-polyphenol capsules for infected full-thickness skin wound healing.

Liu N, Zhu S, Deng Y, Xie M, Zhao M, Sun T Bioact Mater. 2022; 24:69-80.

PMID: 36582352 PMC: 9772805. DOI: 10.1016/j.bioactmat.2022.12.009.

Dihydroartemisinin beneficially regulates splenic immune cell heterogeneity through the SOD3-JNK-AP-1 axis.

Zhang Y, Li Q, Jiang N, Su Z, Yuan Q, Lv L Sci China Life Sci. 2022; 65(8):1636-1654.

PMID: 35226255 DOI: 10.1007/s11427-021-2061-7.

Expression and function of FRA1 protein in tumors.

Jiang X, Xie H, Dou Y, Yuan J, Zeng D, Xiao S Mol Biol Rep. 2019; 47(1):737-752.

PMID: 31612408 DOI: 10.1007/s11033-019-05123-9.

miR-497 suppresses epithelial-mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1.

Zhang N, Shen Q, Zhang P Onco Targets Ther. 2016; 9:6597-6604.

PMID: 27822064 PMC: 5087769. DOI: 10.2147/OTT.S114609.

Fra-1 is a key driver of colon cancer metastasis and a Fra-1 classifier predicts disease-free survival.

Iskit S, Schlicker A, Wessels L, Peeper D Oncotarget. 2015; 6(41):43146-61.

PMID: 26646695 PMC: 4791222. DOI: 10.18632/oncotarget.6454.

References

Zhang Q, Adiseshaiah P, Kalvakolanu D, Reddy S . A Phosphatidylinositol 3-kinase-regulated Akt-independent signaling promotes cigarette smoke-induced FRA-1 expression. J Biol Chem. 2006; 281(15):10174-81. DOI: 10.1074/jbc.M513008200. View

Kjaerheim K, Roe O, Waterboer T, Sehr P, Rizk R, Dai H . Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples. Int J Cancer. 2007; 120(11):2459-65. DOI: 10.1002/ijc.22592. View

Luo Y, Prestwich G . Hyaluronic acid-N-hydroxysuccinimide: a useful intermediate for bioconjugation. Bioconjug Chem. 2001; 12(6):1085-8. DOI: 10.1021/bc015513p. View

Xiao G, Jeffers M, Bellacosa A, Mitsuuchi Y, Woude G, Testa J . Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A. 2001; 98(1):247-52. PMC: 14576. DOI: 10.1073/pnas.98.1.247. View

Nagano O, Saya H . Mechanism and biological significance of CD44 cleavage. Cancer Sci. 2004; 95(12):930-5. PMC: 11159127. DOI: 10.1111/j.1349-7006.2004.tb03179.x. View

Cao H, Dronadula N, Rao G . Thrombin induces expression of FGF-2 via activation of PI3K-Akt-Fra-1 signaling axis leading to DNA synthesis and motility in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2005; 290(1):C172-82. DOI: 10.1152/ajpcell.00284.2005. View

Debinski W, Gibo D . Fos-related antigen 1 modulates malignant features of glioma cells. Mol Cancer Res. 2005; 3(4):237-49. DOI: 10.1158/1541-7786.MCR-05-0004. View

Pettersson T, Froseth B, Riska H, Klockars M . Concentration of hyaluronic acid in pleural fluid as a diagnostic aid for malignant mesothelioma. Chest. 1988; 94(5):1037-9. DOI: 10.1378/chest.94.5.1037. View

Matsui M, Tokuhara M, Konuma Y, Nomura N, Ishizaki R . Isolation of human fos-related genes and their expression during monocyte-macrophage differentiation. Oncogene. 1990; 5(3):249-55. View

10.

Zajchowski D, Bartholdi M, Gong Y, Webster L, Liu H, Munishkin A . Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. Cancer Res. 2001; 61(13):5168-78. View

11.

ROBOZ J, Chahinian A, HOLLAND J, SILIDES D, Szrajer L . Early diagnosis and monitoring of transplanted human malignant mesothelioma by serum hyaluronic acid. J Natl Cancer Inst. 1989; 81(12):924-8. DOI: 10.1093/jnci/81.12.924. View

12.

Fulgenzi G, Graciotti L, Faronato M, Soldovieri M, Miceli F, Amoroso S . Human neoplastic mesothelial cells express voltage-gated sodium channels involved in cell motility. Int J Biochem Cell Biol. 2006; 38(7):1146-59. DOI: 10.1016/j.biocel.2005.12.003. View

13.

Weg-Remers S, Ponta H, Herrlich P, Konig H . Regulation of alternative pre-mRNA splicing by the ERK MAP-kinase pathway. EMBO J. 2001; 20(15):4194-203. PMC: 149173. DOI: 10.1093/emboj/20.15.4194. View

14.

Chiu B, Churg A, Tengblad A, Pearce R, McCAUGHEY W . Analysis of hyaluronic acid in the diagnosis of malignant mesothelioma. Cancer. 1984; 54(10):2195-9. DOI: 10.1002/1097-0142(19841115)54:10<2195::aid-cncr2820541021>3.0.co;2-l. View

15.

Recio J, Merlino G . Hepatocyte growth factor/scatter factor induces feedback up-regulation of CD44v6 in melanoma cells through Egr-1. Cancer Res. 2003; 63(7):1576-82. View

16.

Shukla A, Flanders T, Lounsbury K, Mossman B . The gamma-glutamylcysteine synthetase and glutathione regulate asbestos-induced expression of activator protein-1 family members and activity. Cancer Res. 2004; 64(21):7780-6. DOI: 10.1158/0008-5472.CAN-04-1365. View

17.

Klominek J, Sumitran Karuppan S, Hauzenberger D . Differential motile response of human malignant mesothelioma cells to fibronectin, laminin and collagen type IV: the role of beta1 integrins. Int J Cancer. 1997; 72(6):1034-44. DOI: 10.1002/(sici)1097-0215(19970917)72:6<1034::aid-ijc19>3.0.co;2-4. View

18.

Hu Y, Lam K, Law S, Wong J, Srivastava G . Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC. Clin Cancer Res. 2001; 7(11):3519-25. View

19.

Sneath R, Mangham D . The normal structure and function of CD44 and its role in neoplasia. Mol Pathol. 1999; 51(4):191-200. PMC: 395635. DOI: 10.1136/mp.51.4.191. View

20.

Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad A, Vacek P . Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc Natl Acad Sci U S A. 2006; 103(38):14128-33. PMC: 1599923. DOI: 10.1073/pnas.0604544103. View