Actin depolymerizing factor (ADF)/cofilin, an actin-binding protein ubiquitously expressed in a variety of organisms, is required for regulation of actin dynamics. The activity of ADF/cofilin is dependent on serine 3 phosphorylation by LIM kinase (LIMK), which is regulated by the Rho small GTPase signaling pathway. ADF/cofilin is strongly associated with several important cell biological functions, including cell cycle, morphological maintenance, and locomotion. These functions affect several biological events, including embryogenesis, oncology, nephropathy, and neurodegenerations. Here, we focus on the biochemical and pathophysiological role of ADF/cofilin in mammals. 1. Introduction ADF/cofilin has been reported to be involved in several cellular functions via regulation of actin dynamics. For instance, ADF/cofilin is required for actin reorganization at the contractile ring for cytokinesis and is essential for cell cycle progression. ADF/cofilin regulates actin dynamics through a depolymerization or severing of actin filaments. The only known mechanism for regulating the activity of ADF/cofilin activity is protein phosphorylation. ADF/cofilin becomes inactive when it is phosphorylated at serine 3 residue by LIM kinase (LIMK) or testis-specific kinase (TESK) 1 and 2 [1–3]. For LIMK, a series of signal transduction pathway for ADF/cofilin activity is primarily controlled by Rho family of small GTPase. Cells stimulated by growth factors lead to activation of the receptor tyrosine kinase (RTK) that recruits Rho small GTPase and Rho-associated protein kinase (ROCK) to phosphorylate LIM kinase and subsequent ADF/cofilin [4]. Also, dephosphorylation of ADF/cofilin is mediated by slingshot (SSH) phosphatase, chronophin (CIN) phosphatase, and protein phosphatase 1 and 2A (PP1 and PP2A) [5]. In addition to protein phosphorylation, the activity of ADF/cofilin is also regulated by intracellular pH and its association with phosphatidyl inositol bisphosphate (PIP2) [6]. Recent studies have shown that the activity of ADF/cofilin is increased at the telophase of mitosis to regulate the dynamics of actomyosin-based contractile ring and maintain the cleavage furrow for cell division [7, 8]. In addition to mitotic phase, optimal expression of ADF/cofilin is also critical for G1 to S phase progression. Forced expression of ADF/cofilin can result in G1 phase arrest through destabilization of actin cytoskeleton and upregulation of cell cycle inhibitor p 2 7 k i p 1 [9]. ADF/cofilin is involved in migration, locomotion and metastasis of cancerous cells. It has been
References
[1]
O. Bernard, “Lim kinases, regulators of actin dynamics,” International Journal of Biochemistry and Cell Biology, vol. 39, no. 6, pp. 1071–1076, 2007.
[2]
J. Toshima, J. Y. Toshima, T. Amano, N. Yang, S. Narumiya, and K. Mizuno, “Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation,” Molecular Biology of the Cell, vol. 12, no. 4, pp. 1131–1145, 2001.
[3]
J. Toshima, J. Y. Toshima, K. Takeuchi, R. Mori, and K. Mizuno, “Cofilin phosphorylation and actin reorganization activities of testicular protein kinase 2 and its predominant expression in testicular sertoli cells,” Journal of Biological Chemistry, vol. 276, no. 33, pp. 31449–31458, 2001.
[4]
M. Kobayashi, M. Nishita, T. Mishima, K. Ohashi, and K. Mizuno, “MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration,” EMBO Journal, vol. 25, no. 4, pp. 713–726, 2006.
[5]
T. Takuma, T. Ichida, N. Yokoyama, S. Tamura, and T. Obinata, “Dephosphorylation of cofilin in parotid acinar cells,” Journal of Biochemistry, vol. 120, no. 1, pp. 35–41, 1996.
[6]
J. R. Bamburg and B. W. Bernstein, “ADF/cofilin,” Current Biology, vol. 18, no. 7, pp. R273–R275, 2008.
[7]
N. Kaji, K. Ohashi, M. Shuin, R. Niwa, T. Uemura, and K. Mizuno, “Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells,” Journal of Biological Chemistry, vol. 278, no. 35, pp. 33450–33455, 2003.
[8]
R. M. Warn and R. Magrath, “F-actin distribution during the cellularization of the Drosophila embryo visualized with FL-phalloidin,” Experimental Cell Research, vol. 143, no. 1, pp. 103–114, 1983.
[9]
C. H. Tsai, S. J. Chiu, C. C. Liu et al., “Regulated expression of cofilin and the consequent regulation of p27 kip1 are essential for G1 phase progression,” Cell Cycle, vol. 8, no. 15, pp. 2365–2374, 2009.
[10]
W. Wang, G. Mouneimne, M. Sidani et al., “The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors,” Journal of Cell Biology, vol. 173, no. 3, pp. 395–404, 2006.
[11]
W. Wang, R. Eddy, and J. Condeelis, “The cofilin pathway in breast cancer invasion and metastasis,” Nature Reviews Cancer, vol. 7, no. 6, pp. 429–440, 2007.
[12]
M. Quintela-Fandino, E. Arpaia, D. Brenner et al., “HUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 6, pp. 2622–2627, 2010.
[13]
Y. J. Lee, D. J. Mazzatti, Z. Yun, and P. C. Keng, “Inhibition of invasiveness of human lung cancer cell line H1299 by over-expression of cofilin,” Cell Biology International, vol. 29, no. 11, pp. 877–883, 2005.
[14]
R. Nagaoka, H. Abe, and T. Obinata, “Site-directed mutagenesis of the phosphorylation site of cofilin: its role in cofilin-actin interaction and cytoplasmic localization,” Cell Motility and the Cytoskeleton, vol. 35, no. 3, pp. 200–209, 1996.
[15]
J. R. Bamburg, B. W. Bernstein, R. C. Davis et al., “ADF/Cofilin-actin rods in neurodegenerative diseases,” Current Alzheimer Research, vol. 7, no. 3, pp. 241–250, 2010.
[16]
K. Berger and M. J. Moeller, “Cofilin-1 in the podocyte: a molecular switch for actin dynamics,” International Urology and Nephrology, vol. 43, no. 1, pp. 273–275, 2011.
[17]
M. K. Vartiainen, T. Mustonen, P. K. Mattila et al., “The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics,” Molecular Biology of the Cell, vol. 13, no. 1, pp. 183–194, 2002.
[18]
L. Blanchoin, T. D. Pollard, and R. D. R. D. Mullins, “Interactions of ADF/cofilin, Arp2/3 complex, capping protein and profilin in remodeling of branched actin filament networks,” Current Biology, vol. 10, no. 20, pp. 1273–1282, 2000.
[19]
M. Van Troys, L. Huyck, S. Leyman, S. Dhaese, J. Vandekerkhove, and C. Ampe, “Ins and outs of ADF/cofilin activity and regulation,” European Journal of Cell Biology, vol. 87, no. 8-9, pp. 649–667, 2008.
[20]
B. W. Bernstein and J. R. Bamburg, “ADF/Cofilin: a functional node in cell biology,” Trends in Cell Biology, vol. 20, no. 4, pp. 187–195, 2010.
[21]
M. Oser and J. Condeelis, “The cofilin activity cycle in lamellipodia and invadopodia,” Journal of Cellular Biochemistry, vol. 108, no. 6, pp. 1252–1262, 2009.
[22]
S. Kurita, E. Gunji, K. Ohashi, and K. Mizuno, “Actin filaments-stabilizing and -bundling activities of cofilin-phosphatase Slingshot-1,” Genes to Cells, vol. 12, no. 5, pp. 663–676, 2007.
[23]
N. Marcoux and K. Vuori, “EGF receptor activity is essential for adhesion-induced stress fiber formation and cofilin phosphorylation,” Cellular Signalling, vol. 17, no. 11, pp. 1449–1455, 2005.
[24]
N. S. Bryce, G. Schevzov, V. Ferguson et al., “Specification of actin filament function and molecular composition by tropomyosin isoforms,” Molecular Biology of the Cell, vol. 14, no. 3, pp. 1002–1016, 2003.
[25]
P. Gunning, G. O'Neill, and E. Hardeman, “Tropomyosin-based regulation of the actin cytoskeleton in time and space,” Physiological Reviews, vol. 88, no. 1, pp. 1–35, 2008.
[26]
K. Katoh, Y. Kano, M. Amano, K. Kaibuchi, and K. Fujiwara, “Stress fiber organization regulated by MLCK and Rho-kinase in cultured human fibroblasts,” American Journal of Physiology, vol. 280, no. 6, pp. C1669–C1679, 2001.
[27]
J. R. Molina and A. A. Adjei, “The Ras/Raf/MAPK pathway,” Journal of Thoracic Oncology, vol. 1, no. 1, pp. 7–9, 2006.
[28]
W. Kolch, “Coordinating ERK/MAPK signalling through scaffolds and inhibitors,” Nature Reviews Molecular Cell Biology, vol. 6, no. 11, pp. 827–837, 2005.
[29]
J. Paez and W. R. Sellers, “PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling,” Cancer Treatment and Research, vol. 115, pp. 145–167, 2003.
[30]
G. H. Wabnitz, G. Nebl, M. Klemke, A. J. Schr？der, and Y. Samstag, “Phosphatidylinositol 3-kinase functions as a Ras effector in the signaling cascade that regulates dephosphorylation of the actin-remodeling protein cofilin after costimulation of untransformed human T lymphocytes,” Journal of Immunology, vol. 176, no. 3, pp. 1668–1674, 2006.
[31]
D. T. Denhardt, “Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signalling,” Biochemical Journal, vol. 318, no. 3, pp. 729–747, 1996.
[32]
S. H. Zigmond, “Signal transduction and actin filament organization,” Current Opinion in Cell Biology, vol. 8, no. 1, pp. 66–73, 1996.
[33]
S. Arber, F. A. Barbayannis, H. Hanser et al., “Regulation of actin dynamics through phosphorylation of cofilin by LIM- kinase,” Nature, vol. 393, no. 6687, pp. 805–809, 1998.
[34]
T. Y. Huang, C. Dermardirossian, and G. M. Bokoch, “Cofilin phosphatases and regulation of actin dynamics,” Current Opinion in Cell Biology, vol. 18, no. 1, pp. 26–31, 2006.
[35]
R. Niwa, K. Nagata-Ohashi, M. Takeichi, K. Mizuno, and T. Uemura, “Control of actin reorganization by slingshot, a family of phosphatases that dephosphorylate ADF/cofilin,” Cell, vol. 108, no. 2, pp. 233–246, 2002.
[36]
Y. Yoo, H. J. Ho, C. Wang, and J. L. Guan, “Tyrosine phosphorylation of cofilin at Y68 by v-Src leads to its degradation through ubiquitin-proteasome pathway,” Oncogene, vol. 29, no. 2, pp. 263–272, 2010.
[37]
M. De Graauw, I. Tijdens, M. B. Smeets, P. J. Hensbergen, A. M. Deelder, and B. Van De Water, “Annexin A2 phosphorylation mediates cell scattering and branching morphogenesis via cofilin activation,” Molecular and Cellular Biology, vol. 28, no. 3, pp. 1029–1040, 2008.
[38]
U. Rescher, C. Ludwig, V. Konietzko, A. Kharitonenkov, and V. Gerke, “Tyrosine phosphorylation of annexin A2 regulates Rho-mediated actin rearrangement and cell adhesion,” Journal of Cell Science, vol. 121, no. 13, pp. 2177–2185, 2008.
[39]
Y. J. Lee and P. C. Keng, “Studying the effects of actin cytoskeletal destabilization on cell cycle by cofilin overexpression,” Molecular Biotechnology, vol. 31, no. 1, pp. 1–10, 2005.
[40]
G. C. Bellenchi, C. B. Gurniak, E. Perlas, S. Middei, M. Ammassari-Teule, and W. Witke, “N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex,” Genes and Development, vol. 21, no. 18, pp. 2347–2357, 2007.
[41]
M. S. Crane, J. B. Clarke, and D. B. Thomas, “Cell cycle dependent changes in morphology. Studies with a cold sensitive mutant of Chinese hamster ovary cells,” Experimental Cell Research, vol. 107, no. 1, pp. 89–94, 1977.
[42]
A. G. Clark and E. Paluch, “Mechanics and regulation of cell shape during the cell cycle,” Results and Problems in Cell Differentiation, vol. 53, pp. 31–73, 2011.
[43]
P. K. Hepler, A. Valster, T. Molchan, and J. W. Vos, “Roles for Kinesin and myosin during cytokinesis,” Philosophical Transactions of the Royal Society B, vol. 357, no. 1422, pp. 761–766, 2002.
[44]
M. D. Larrea, F. Hong, S. A. Wander et al., “RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 23, pp. 9268–9273, 2009.
[45]
A. Van Opstal, J. J. M. Bijvelt, C. Margadant, and J. Boonstra, “Role of signal transduction and actin in G1 phase progression,” Advances in Enzyme Regulation, vol. 45, pp. 186–200, 2005.
[46]
N. Kaji, A. Muramoto, and K. Mizuno, “LIM kinase-mediated cofilin phosphorylation during mitosis is required for precise spindle positioning,” Journal of Biological Chemistry, vol. 283, no. 8, pp. 4983–4992, 2008.
[47]
F. F. Hsu, T. Y. Lin, J. Y. Chen, and S. Y. Shieh, “P53-mediated transactivation of LIMK2b links actin dynamics to cell cycle checkpoint control,” Oncogene, vol. 29, no. 19, pp. 2864–2876, 2010.
[48]
M. Davila, D. Jhala, D. Ghosh, W. E. Grizzle, and R. Chakrabarti, “Expression of LIM kinase 1 is associated with reversible G1/S phase arrest, chromosomal instability and prostate cancer,” Molecular Cancer, vol. 6, article 40, 2007.
[49]
A. Amiri, F. Noei, T. Feroz, and J. M. Lee, “Geldanamycin anisimycins activate rho and stimulate rho- and ROCK-dependent actin stress fiber formation,” Molecular Cancer Research, vol. 5, no. 9, pp. 933–942, 2007.
[50]
Y.-P. Ho, C.-W. Kuo, Y.-T. Hsu et al., “β-Actin is a downstream effector of the PI3K/AKT signaling pathway in myeloma cells,” Molecular and Cellular Biochemistry, vol. 348, no. 1-2, pp. 129–139, 2011.
[51]
H. Chen, J. Bai, J. Ye et al., “JWA as a functional molecule to regulate cancer cells migration via MAPK cascades and F-actin cytoskeleton,” Cellular Signalling, vol. 19, no. 6, pp. 1315–1327, 2007.
[52]
E. H. J. Danen, P. Sonneveld, A. Sonnenberg, and K. M. Yamada, “Dual stimulation of Ras/Mitogen-activated protein kinase and RhoA by cell adhesion to fibronectin supports growth factor-stimulated cell cycle progression,” Journal of Cell Biology, vol. 151, no. 7, pp. 1413–1422, 2000.
[53]
B. Geiger, A. Bershadsky, R. Pankov, and K. M. Yamada, “Transmembrane extracellular matrix-cytoskeleton crosstalk,” Nature Reviews Molecular Cell Biology, vol. 2, no. 11, pp. 793–805, 2001.
[54]
M. Maekawa, T. Ishizaki, S. Boku et al., “Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase,” Science, vol. 285, no. 5429, pp. 895–898, 1999.
[55]
E. D. Schejter, “Actin organization in the early Drosophila embryo,” Novartis Foundation Symposium, vol. 269, pp. 127–138, 2005.
[56]
K. Schwarzerova, Z. Vondrakova, L. Fischer et al., “The role of actin isoforms in somatic embryogenesis in Norway spruce,” BMC Plant Biology, vol. 10, article 89, 2010.
[57]
D. L. Kropf, S. K. Berge, and R. S. Quatrano, “Actin localization during fucus embryogenesis,” Plant Cell, vol. 1, no. 2, pp. 191–200, 1989.
[58]
M. Ma, L. Zhou, X. Guo et al., “Decreased cofilin1 expression is important for compaction during early mouse embryo development,” Biochimica et Biophysica Acta, vol. 1793, no. 12, pp. 1804–1810, 2009.
[59]
J. R. Bamburg and G. S. Bloom, “Cytoskeletal pathologies of Alzheimer disease,” Cell Motility and the Cytoskeleton, vol. 66, no. 8, pp. 635–649, 2009.
[60]
R. C. Davis, R. Furukawa, and M. Fechheimer, “A cell culture model for investigation of Hirano bodies,” Acta Neuropathologica, vol. 115, no. 2, pp. 205–217, 2008.
[61]
L. S. Minamide, A. M. Striegl, J. A. Boyle, P. J. Meberg, and J. R. Bamburg, “Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function,” Nature Cell Biology, vol. 2, no. 9, pp. 628–636, 2000.
[62]
M. E. Velasco, M. A. Smith, S. L. Siedlak, A. Nunomura, and G. Perry, “Striation is the characteristic neuritic abnormality in Alzheimer disease,” Brain Research, vol. 813, no. 2, pp. 329–333, 1998.
[63]
M. T. Maloney and J. R. Bamburg, “Cofilin-mediated neurodegeneration in Alzheimer's disease and other amyloidopathies,” Molecular Neurobiology, vol. 35, no. 1, pp. 21–43, 2007.
[64]
P. Garg, R. Verma, L. Cook et al., “Actin-depolymerizing factor cofilin-1 is necessary in maintaining mature podocyte architecture,” Journal of Biological Chemistry, vol. 285, no. 29, pp. 22676–22688, 2010.
[65]
P. Mundel, J. Reiser, A. Z. M. Borja et al., “Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalized mouse podocyte cell lines,” Experimental Cell Research, vol. 236, no. 1, pp. 248–258, 1997.
[66]
W. E. Smoyer and P. Mundel, “Regulation of podocyte structure during the development of nephrotic syndrome,” Journal of Molecular Medicine, vol. 76, no. 3-4, pp. 172–183, 1998.
[67]
C. Faul, K. Asanuma, E. Yanagida-Asanuma, K. Kim, and P. Mundel, “Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton,” Trends in Cell Biology, vol. 17, no. 9, pp. 428–437, 2007.
[68]
P. Mundel and J. Reiser, “Proteinuria: an enzymatic disease of the podocyte,” Kidney International, vol. 77, no. 7, pp. 571–580, 2010.
[69]
D. Kerjaschki, “Caught flat-footed: podocyte damage and the molecular bases of focal glomerulosclerosis,” Journal of Clinical Investigation, vol. 108, no. 11, pp. 1583–1587, 2001.
[70]
S. Ashworth, B. Teng, J. Kaufeld et al., “Cofilin-1 inactivation leads to proteinuria—studies in zebrafish, mice and humans,” PLoS ONE, vol. 5, no. 9, Article ID e12626, pp. 1–10, 2010.
[71]
J. M. Kaplan, S. H. Kim, K. N. North et al., “Mutations in ACTN4, encoding α-actinin-4, cause familial focal segmental glomerulosclerosis,” Nature Genetics, vol. 24, no. 3, pp. 251–256, 2000.
[72]
M. Kestil？, U. Lenkkeri, M. M？nnikk？ et al., “Positionally cloned gene for a novel glomerular protein—Nephrin—is mutated in congenital nephrotic syndrome,” Molecular Cell, vol. 1, no. 4, pp. 575–582, 1998.
[73]
N. Boute, O. Gribouval, S. Roselli et al., “NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome,” Nature Genetics, vol. 24, no. 4, pp. 349–354, 2000.
[74]
J. Y. Rao and N. Li, “Microfilament actin remodeling as a potential target for cancer drug development,” Current Cancer Drug Targets, vol. 4, no. 4, pp. 345–354, 2004.
[75]
T. T. Bonello, J. R. Stehn, and P. W. Gunning, “New approaches to targeting the actin cytoskeleton for chemotherapy,” Future Medicinal Chemistry, vol. 1, no. 7, pp. 1311–1331, 2009.
[76]
D. H. Lee, G. B. Iwanski, and N. H. Thoennissen, “Cucurbitacin: ancient compound shedding new light on cancer treatment,” TheScientificWorldJournal, vol. 10, pp. 413–418, 2010.
[77]
D. A. Knecht, R. A. LaFleur, A. W. Kahsai, C. E. Argueta, A. B. Beshir, and G. Fenteany, “Cucurbitacin I Inhibits cell motility by indirectly interfering with actin dynamics,” PLoS ONE, vol. 5, no. 11, Article ID e14039, 2010.
[78]
T. Tannin-Spitz, S. Grossman, S. Dovrat, H. E. Gottlieb, and M. Bergman, “Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells,” Biochemical Pharmacology, vol. 73, no. 1, pp. 56–67, 2007.
[79]
D. Yin, N. Wakimoto, H. Xing et al., “Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme,” International Journal of Cancer, vol. 123, no. 6, pp. 1364–1375, 2008.
[80]
K. L. K. Duncan, M. D. Duncan, M. C. Alley, and E. A. Sausville, “Cucurbitacin E-induced disruption of the actin and vimentin cytoskeleton in prostate carcinoma cells,” Biochemical Pharmacology, vol. 52, no. 10, pp. 1553–1560, 1996.
[81]
K. A. El Sayed, M. A. Khanfar, H. M. Shallal et al., “Latrunculin A and its C-17-O-carbamates inhibit prostate tumor cell invasion and HIF-1 activation in breast tumor cells,” Journal of Natural Products, vol. 71, no. 3, pp. 396–402, 2008.
[82]
J. I. Chao and H. F. Liu, “The blockage of survivin and securin expression increases the cytochalasin B-induced cell death and growth inhibition in human cancer cells,” Molecular Pharmacology, vol. 69, no. 1, pp. 154–164, 2006.
[83]
H. Takeuchi, G. Ara, E. A. Sausville, and B. Teicher, “Jasplakinolide: interaction with radiation and hyperthermia in human prostate carcinoma and Lewis lung carcinoma,” Cancer Chemotherapy and Pharmacology, vol. 42, no. 6, pp. 491–496, 1998.
[84]
K. Nagata-Ohashi, Y. Ohta, K. Goto et al., “A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia,” Journal of Cell Biology, vol. 165, no. 4, pp. 465–471, 2004.
[85]
Y. J. Lee, T. J. Sheu, and P. C. Keng, “Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin,” Biochemical and Biophysical Research Communications, vol. 335, no. 2, pp. 286–291, 2005.
[86]
P. Hotulainen, E. Paunola, M. K. Vartiainen, and P. Lappalainen, “Actin-depolymerizing factor and cofilin-1 play overlapping roles in promoting rapid F-actin depolymerization in mammalian nonmuscle cells,” Molecular Biology of the Cell, vol. 16, no. 2, pp. 649–664, 2005.
[87]
N. Zebda, O. Bernard, M. Bailly, S. Welti, D. S. Lawrence, and J. S. Condeelis, “Phosphorylation of ADF/cofilin abolishes EGF-induced actin nucleation at the leading edge and subsequent lamellipod extension,” Journal of Cell Biology, vol. 151, no. 5, pp. 1119–1127, 2000.
[88]
B. V. McConnell, K. Koto, and A. Gutierrez-Hartmann, “Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression,” Molecular Cancer, vol. 10, article 75, 2011.
[89]
D. H. Vlecken and C. P. Bagowski, “LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells,” Zebrafish, vol. 6, no. 4, pp. 433–439, 2009.
[90]
K. Borensztajn, M. P. Peppelenbosch, and C. A. Spek, “Coagulation Factor Xa inhibits cancer cell migration via LIMK1-mediated cofilin inactivation,” Thrombosis Research, vol. 125, no. 6, pp. e323–e328, 2010.
[91]
T. Ahmed, K. Shea, J. R. W. Masters, G. E. Jones, and C. M. Wells, “A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF,” Cellular Signalling, vol. 20, no. 7, pp. 1320–1328, 2008.
[92]
C. T. Yap, T. I. Simpson, T. Pratt, D. J. Price, and S. K. Maciver, “The motility of glioblastoma tumour cells is modulated by intracellular cofilin expression in a concentration-dependent manner,” Cell Motility and the Cytoskeleton, vol. 60, no. 3, pp. 153–165, 2005.
[93]
J. Van Rheenen, X. Song, W. Van Roosmalen et al., “EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells,” Journal of Cell Biology, vol. 179, no. 6, pp. 1247–1259, 2007.
