Invasive Matrix Degradation at Focal Adhesions Occurs Via Protease Recruitment by a FAK-p130Cas Complex

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2012 Feb 1

PMID 22291036

Citations 121

Authors

Yu Wang

Mark A McNiven

Affiliations

Soon will be listed here.

Abstract

Tumor cell migration and the concomitant degradation of extracellular matrix (ECM) are two essential steps in the metastatic process. It is well established that focal adhesions (FAs) play an important role in regulating migration; however, whether these structures contribute to matrix degradation is not clear. In this study, we report that multiple cancer cell lines display degradation of ECM at FA sites that requires the targeted action of MT1-MMP. Importantly, we have found that this MT1-MMP targeting is dependent on an association with a FAK-p130Cas complex situated at FAs and is regulated by Src-mediated phosphorylation of Tyr 573 at the cytoplasmic tail of MT1. Disrupting the FAK-p130Cas-MT1 complex significantly impairs FA-mediated degradation and tumor cell invasion yet does not appear to affect invadopodia formation or function. These findings demonstrate a novel function for FAs and also provide molecular insights into MT1-MMP targeting and function.

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References

Wolf K, Friedl P . Mapping proteolytic cancer cell-extracellular matrix interfaces. Clin Exp Metastasis. 2008; 26(4):289-98. DOI: 10.1007/s10585-008-9190-2. View

Ueda J, Kajita M, Suenaga N, Fujii K, Seiki M . Sequence-specific silencing of MT1-MMP expression suppresses tumor cell migration and invasion: importance of MT1-MMP as a therapeutic target for invasive tumors. Oncogene. 2003; 22(54):8716-22. DOI: 10.1038/sj.onc.1206962. View

Wu X, Gan B, Yoo Y, Guan J . FAK-mediated src phosphorylation of endophilin A2 inhibits endocytosis of MT1-MMP and promotes ECM degradation. Dev Cell. 2005; 9(2):185-96. DOI: 10.1016/j.devcel.2005.06.006. View

Uekita T, Gotoh I, Kinoshita T, Itoh Y, Sato H, Shiomi T . Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1 is a new member of the Cupin superfamily. A possible multifunctional protein acting as an invasion suppressor down-regulated in tumors. J Biol Chem. 2004; 279(13):12734-43. DOI: 10.1074/jbc.M309957200. View

Hauck C, Hsia D, Puente X, Cheresh D, Schlaepfer D . FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth. EMBO J. 2002; 21(23):6289-302. PMC: 136935. DOI: 10.1093/emboj/cdf631. View

Stylli S, Kaye A, Lock P . Invadopodia: at the cutting edge of tumour invasion. J Clin Neurosci. 2008; 15(7):725-37. DOI: 10.1016/j.jocn.2008.03.003. View

Coopman P, Do M, Thompson E, Mueller S . Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity. Clin Cancer Res. 1998; 4(2):507-15. View

Fraley S, Feng Y, Krishnamurthy R, Kim D, Celedon A, Longmore G . A distinctive role for focal adhesion proteins in three-dimensional cell motility. Nat Cell Biol. 2010; 12(6):598-604. PMC: 3116660. DOI: 10.1038/ncb2062. View

Cukierman E, Pankov R, Yamada K . Cell interactions with three-dimensional matrices. Curr Opin Cell Biol. 2002; 14(5):633-9. DOI: 10.1016/s0955-0674(02)00364-2. View

10.

Kubow K, Horwitz A . Reducing background fluorescence reveals adhesions in 3D matrices. Nat Cell Biol. 2010; 13(1):3-5. PMC: 3083631. DOI: 10.1038/ncb0111-3. View

11.

Cunningham-Edmondson A, Hanks S . p130Cas substrate domain signaling promotes migration, invasion, and survival of estrogen receptor-negative breast cancer cells. Breast Cancer (Dove Med Press). 2013; 1:39-52. PMC: 3022348. DOI: 10.2147/bctt.s6255. View

12.

Hamadi A, Bouali M, Dontenwill M, Stoeckel H, Takeda K, Ronde P . Regulation of focal adhesion dynamics and disassembly by phosphorylation of FAK at tyrosine 397. J Cell Sci. 2005; 118(Pt 19):4415-25. DOI: 10.1242/jcs.02565. View

13.

Sato H, Takino T, Miyamori H . Roles of membrane-type matrix metalloproteinase-1 in tumor invasion and metastasis. Cancer Sci. 2005; 96(4):212-7. PMC: 11158816. DOI: 10.1111/j.1349-7006.2005.00039.x. View

14.

Cukierman E, Pankov R, Stevens D, Yamada K . Taking cell-matrix adhesions to the third dimension. Science. 2001; 294(5547):1708-12. DOI: 10.1126/science.1064829. View

15.

Mitra S, Hanson D, Schlaepfer D . Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005; 6(1):56-68. DOI: 10.1038/nrm1549. View

16.

Ezratty E, Partridge M, Gundersen G . Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol. 2005; 7(6):581-90. DOI: 10.1038/ncb1262. View

17.

Buccione R, Caldieri G, Ayala I . Invadopodia: specialized tumor cell structures for the focal degradation of the extracellular matrix. Cancer Metastasis Rev. 2009; 28(1-2):137-49. DOI: 10.1007/s10555-008-9176-1. View

18.

Caldieri G, Ayala I, Attanasio F, Buccione R . Cell and molecular biology of invadopodia. Int Rev Cell Mol Biol. 2009; 275:1-34. DOI: 10.1016/S1937-6448(09)75001-4. View

19.

Linder S, Aepfelbacher M . Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol. 2003; 13(7):376-85. DOI: 10.1016/s0962-8924(03)00128-4. View

20.

Caldieri G, Buccione R . Aiming for invadopodia: organizing polarized delivery at sites of invasion. Trends Cell Biol. 2009; 20(2):64-70. DOI: 10.1016/j.tcb.2009.10.006. View