Targeting ADAM-mediated Ligand Cleavage to Inhibit HER3 and EGFR Pathways in Non-small Cell Lung Cancer

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2006 Jul 18

PMID 16843264

Citations 179

Authors

Bin-Bing S Zhou

Michael Peyton

Biao He

Changnian Liu

Luc Girard

Eian Caudler

Yvonne Lo

Frederic Baribaud

Iwao Mikami

Noemi Reguart

Gengjie Yang

Yanlong Li

Wenqing Yao

Kris Vaddi

Adi F Gazdar

Steven M Friedman

David M Jablons

Robert C Newton

Jordan S Fridman

John D Minna

Peggy A Scherle

Affiliations

Soon will be listed here.

Abstract

We describe here the existence of a heregulin-HER3 autocrine loop, and the contribution of heregulin-dependent, HER2-mediated HER3 activation to gefitinib insensitivity in non-small cell lung cancer (NSCLC). ADAM17 protein, a major ErbB ligand sheddase, is upregulated in NSCLC and is required not only for heregulin-dependent HER3 signaling, but also for EGFR ligand-dependent signaling in NSCLC cell lines. A selective ADAM inhibitor, INCB3619, prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. These results show that ADAM inhibition affects multiple ErbB pathways in NSCLC and thus offers an excellent opportunity for pharmacological intervention, either alone or in combination with other drugs.

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References

Kim H, Sierke S, Koland J . Epidermal growth factor-dependent association of phosphatidylinositol 3-kinase with the erbB3 gene product. J Biol Chem. 1994; 269(40):24747-55. View

Valenzuela D, Groffen J . Four human carcinoma cell lines with novel mutations in position 12 of c-K-ras oncogene. Nucleic Acids Res. 1986; 14(2):843-52. PMC: 339468. DOI: 10.1093/nar/14.2.843. View

Peschon J, Slack J, Reddy P, Stocking K, Sunnarborg S, Lee D . An essential role for ectodomain shedding in mammalian development. Science. 1998; 282(5392):1281-4. DOI: 10.1126/science.282.5392.1281. View

Mosesson Y, Yarden Y . Oncogenic growth factor receptors: implications for signal transduction therapy. Semin Cancer Biol. 2004; 14(4):262-70. DOI: 10.1016/j.semcancer.2004.04.005. View

Liu X, Fridman J, Wang Q, Caulder E, Yang G, Covington M . Selective inhibition of ADAM metalloproteases blocks HER-2 extracellular domain (ECD) cleavage and potentiates the anti-tumor effects of trastuzumab. Cancer Biol Ther. 2006; 5(6):648-56. DOI: 10.4161/cbt.5.6.2707. View

Carpenter G, Cohen S . Epidermal growth factor. J Biol Chem. 1990; 265(14):7709-12. View

Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J . TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO J. 2003; 22(5):1114-24. PMC: 150344. DOI: 10.1093/emboj/cdg111. View

Roghani M, Becherer J, Moss M, Atherton R, Erdjument-Bromage H, Arribas J . Metalloprotease-disintegrin MDC9: intracellular maturation and catalytic activity. J Biol Chem. 1999; 274(6):3531-40. DOI: 10.1074/jbc.274.6.3531. View

Herbst R, Fukuoka M, Baselga J . Gefitinib--a novel targeted approach to treating cancer. Nat Rev Cancer. 2004; 4(12):956-65. DOI: 10.1038/nrc1506. View

10.

Jemal A, Murray T, Ward E, Samuels A, Tiwari R, Ghafoor A . Cancer statistics, 2005. CA Cancer J Clin. 2005; 55(1):10-30. DOI: 10.3322/canjclin.55.1.10. View

11.

Blobel C . ADAMs: key components in EGFR signalling and development. Nat Rev Mol Cell Biol. 2005; 6(1):32-43. DOI: 10.1038/nrm1548. View

12.

O-Charoenrat P, Rhys-Evans P, Eccles S . A synthetic matrix metalloproteinase inhibitor prevents squamous carcinoma cell proliferation by interfering with epidermal growth factor receptor autocrine loops. Int J Cancer. 2002; 100(5):527-33. DOI: 10.1002/ijc.10531. View

13.

Bachman K, Herman J, Corn P, Merlo A, Costello J, Cavenee W . Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res. 1999; 59(4):798-802. View

14.

Mendelsohn J . Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clin Cancer Res. 1999; 3(12 Pt 2):2703-7. View

15.

Tracy S, Mukohara T, Hansen M, Meyerson M, Johnson B, Janne P . Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Res. 2004; 64(20):7241-4. DOI: 10.1158/0008-5472.CAN-04-1905. View

16.

Cappuzzo F, Toschi L, Domenichini I, Bartolini S, Ceresoli G, Rossi E . HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients. Br J Cancer. 2005; 93(12):1334-40. PMC: 2361531. DOI: 10.1038/sj.bjc.6602865. View

17.

Yan Y, Shirakabe K, Werb Z . The metalloprotease Kuzbanian (ADAM10) mediates the transactivation of EGF receptor by G protein-coupled receptors. J Cell Biol. 2002; 158(2):221-6. PMC: 2173139. DOI: 10.1083/jcb.200112026. View

18.

Dong J, Opresko L, Dempsey P, Lauffenburger D, Coffey R, Wiley H . Metalloprotease-mediated ligand release regulates autocrine signaling through the epidermal growth factor receptor. Proc Natl Acad Sci U S A. 1999; 96(11):6235-40. PMC: 26865. DOI: 10.1073/pnas.96.11.6235. View

19.

Montero J, Yuste L, Diaz-Rodriguez E, Esparis-Ogando A, Pandiella A . Differential shedding of transmembrane neuregulin isoforms by the tumor necrosis factor-alpha-converting enzyme. Mol Cell Neurosci. 2000; 16(5):631-48. DOI: 10.1006/mcne.2000.0896. View

20.

Baselga J, Arribas J . Metalloprotease-dependent protransforming growth factor-alpha ectodomain shedding in the absence of tumor necrosis factor-alpha-converting enzyme. J Biol Chem. 2001; 276(51):48510-7. DOI: 10.1074/jbc.M103488200. View