LIMK Regulates Tumor-Cell Invasion and Matrix Degradation Through Tyrosine Phosphorylation of MT1-MMP

Overview

Journal Sci Rep

Specialty Science

Date 2016 Apr 28

PMID 27116935

Citations 43

Authors

Emilie Lagoutte

Clementine Villeneuve

Laurence Lafanechere

Claire M Wells

Gareth E Jones

Philippe Chavrier

Carine Rosse

Affiliations

Soon will be listed here.

Abstract

During their metastatic spread, cancer cells need to remodel the extracellular matrix in order to migrate through stromal compartments adjacent to the primary tumor. Dissemination of breast carcinoma cells is mediated by membrane type 1-matrix metalloproteinase (MT1-MMP/MMP14), the main invadopodial matrix degradative component. Here, we identify MT1-MMP as a novel interacting partner of dual-specificity LIM Kinase-1 and -2 (LIMK1/2), and provide several evidence for phosphorylation of tyrosine Y573 in the cytoplasmic domain of MT1-MMP by LIMK. Phosphorylation of Y573 influences association of F-actin binding protein cortactin to MT1-MMP-positive endosomes and invadopodia formation and matrix degradation. Moreover, we show that LIMK1 regulates cortactin association to MT1-MMP-positive endosomes, while LIMK2 controls invadopodia-associated cortactin. In turn, LIMK1 and LIMK2 are required for MT1-MMP-dependent matrix degradation and cell invasion in a three-dimensional type I collagen environment. This novel link between LIMK1/2 and MT1-MMP may have important consequences for therapeutic control of breast cancer cell invasion.

Citing Articles

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References

Belkin A, Akimov S, Zaritskaya L, Ratnikov B, Deryugina E, Strongin A . Matrix-dependent proteolysis of surface transglutaminase by membrane-type metalloproteinase regulates cancer cell adhesion and locomotion. J Biol Chem. 2001; 276(21):18415-22. DOI: 10.1074/jbc.M010135200. View

Rosse C, Lodillinsky C, Fuhrmann L, Nourieh M, Monteiro P, Irondelle M . Control of MT1-MMP transport by atypical PKC during breast-cancer progression. Proc Natl Acad Sci U S A. 2014; 111(18):E1872-9. PMC: 4020077. DOI: 10.1073/pnas.1400749111. View

Jiang A, Lehti K, Wang X, Weiss S, Keski-Oja J, Pei D . Regulation of membrane-type matrix metalloproteinase 1 activity by dynamin-mediated endocytosis. Proc Natl Acad Sci U S A. 2001; 98(24):13693-8. PMC: 61103. DOI: 10.1073/pnas.241293698. View

Uekita T, Itoh Y, Yana I, Ohno H, Seiki M . Cytoplasmic tail-dependent internalization of membrane-type 1 matrix metalloproteinase is important for its invasion-promoting activity. J Cell Biol. 2002; 155(7):1345-56. PMC: 2199326. DOI: 10.1083/jcb.200108112. View

Egeblad M, Werb Z . New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002; 2(3):161-74. DOI: 10.1038/nrc745. View

Nourry C, Grant S, Borg J . PDZ domain proteins: plug and play!. Sci STKE. 2003; 2003(179):RE7. DOI: 10.1126/stke.2003.179.re7. View

Friedl P, Wolf K . Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003; 3(5):362-74. DOI: 10.1038/nrc1075. View

Hotary K, Allen E, Brooks P, Datta N, Long M, Weiss S . Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell. 2003; 114(1):33-45. DOI: 10.1016/s0092-8674(03)00513-0. View

Wang P, Wang X, Pei D . Mint-3 regulates the retrieval of the internalized membrane-type matrix metalloproteinase, MT5-MMP, to the plasma membrane by binding to its carboxyl end motif EWV. J Biol Chem. 2004; 279(19):20461-70. DOI: 10.1074/jbc.M400264200. View

10.

Buccione R, Orth J, McNiven M . Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nat Rev Mol Cell Biol. 2004; 5(8):647-57. DOI: 10.1038/nrm1436. View

11.

Okada A, Bellocq J, Rouyer N, Chenard M, Rio M, Chambon P . Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci U S A. 1995; 92(7):2730-4. PMC: 42292. DOI: 10.1073/pnas.92.7.2730. View

12.

Proschel C, Blouin M, Gutowski N, Ludwig R, Noble M . Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro. Oncogene. 1995; 11(7):1271-81. View

13.

Deak P, Omar M, Saunders R, Pal M, Komonyi O, Szidonya J . P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F. Genetics. 1997; 147(4):1697-722. PMC: 1208341. DOI: 10.1093/genetics/147.4.1697. View

14.

Yamaguchi H, Lorenz M, Kempiak S, Sarmiento C, Coniglio S, Symons M . Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. J Cell Biol. 2005; 168(3):441-52. PMC: 2171731. DOI: 10.1083/jcb.200407076. View

15.

Sibarita J . Deconvolution microscopy. Adv Biochem Eng Biotechnol. 2005; 95:201-43. DOI: 10.1007/b102215. View

16.

Jiang W, Davies G, Martin T, Parr C, Watkins G, Mason M . Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells. Int J Mol Med. 2006; 17(4):583-90. View

17.

Artym V, Zhang Y, Seillier-Moiseiwitsch F, Yamada K, Mueller S . Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Cancer Res. 2006; 66(6):3034-43. DOI: 10.1158/0008-5472.CAN-05-2177. View

18.

Bagheri-Yarmand R, Mazumdar A, Sahin A, Kumar R . LIM kinase 1 increases tumor metastasis of human breast cancer cells via regulation of the urokinase-type plasminogen activator system. Int J Cancer. 2005; 118(11):2703-10. DOI: 10.1002/ijc.21650. View

19.

Hotary K, Li X, Allen E, Stevens S, Weiss S . A cancer cell metalloprotease triad regulates the basement membrane transmigration program. Genes Dev. 2006; 20(19):2673-86. PMC: 1578694. DOI: 10.1101/gad.1451806. View

20.

Lamprecht M, Sabatini D, Carpenter A . CellProfiler: free, versatile software for automated biological image analysis. Biotechniques. 2007; 42(1):71-5. DOI: 10.2144/000112257. View