Targeting ROCK/LIMK/cofilin signaling pathway in cancer

Archives of Pharmacal Research - Tập 42 - Trang 481-491 - 2019
Mee-Hyun Lee1,2, Joydeb Kumar Kundu3, Jung-Il Chae4, Jung-Hyun Shim2,5
1Basic Medical College, Zhengzhou University, Zhengzhou, China
2China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
3Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, Canada
4Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Chonju, Republic of Korea
5Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, Republic of Korea

Tóm tắt

Rho-associated coiled-coil-containing protein kinase (ROCK)/Lin11, Isl-1 and Mec-3 kinase (LIMK)/cofilin-signaling cascades are stimulated by receptor tyrosine kinases, G protein-coupled receptors, integrins and its ligands, growth factors, hormones, fibronectin, collagen, and laminin. Activated signaling cascades can cause transit from normal cells to cancer cells by modulating actin/filament dynamics. In various cancers including breast, prostate, and colorectal cancers, high expression or activity of each cascade protein is significantly associated with poor survival rate of patients as well as aggressive metastasis. Silencing ROCK, LIMK, or cofilin can abrogate their activities and inhibit cancer cell growth, invasion, and metastasis. Therefore ROCK/LIMK/cofilin signaling proteins might be good candidates to develop cancer prevention strategies or therapeutics. Currently, netarsudil, a ROCK inhibitor, is only used in clinical patients for glaucoma or ocular hypertension, but not for cancer. In this review, we will discuss comprehensive ROCK/LIMK/cofilin signaling pathway in cancers and its inhibitors for developing cancer therapy.

Tài liệu tham khảo

Abe H, Kamai T, Hayashi K, Anzai N, Shirataki H, Mizuno T, Yamaguchi Y, Masuda A, Yuki H, Betsunoh H, Yashi M, Fukabori Y, Yoshida K (2014) The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells. BMC Cancer 14:412 Aggelou H, Chadla P, Nikou S, Karteri S, Maroulis I, Kalofonos HP, Papadaki H, Bravou V (2018) LIMK/cofilin pathway and slingshot are implicated in human colorectal cancer progression and chemoresistance. Virchows Arch 472:727–737 Alhopuro P, Sammalkorpi H, Niittymaki I, Bistrom M, Raitila A, Saharinen J, Nousiainen K, Lehtonen HJ, Heliovaara E, Puhakka J, Tuupanen S, Sousa S, Seruca R, Ferreira AM, Hofstra RM, Mecklin JP, Jarvinen H, Ristimaki A, Orntoft TF, Hautaniemi S, Arango D, Karhu A, Aaltonen LA (2012) Candidate driver genes in microsatellite-unstable colorectal cancer. Int J Cancer 130:1558–1566 Amin E, Dubey BN, Zhang SC, Gremer L, Dvorsky R, Moll JM, Taha MS, Nagel-Steger L, Piekorz RP, Somlyo AV, Ahmadian MR (2013) Rho-kinase: regulation, (dys)function, and inhibition. Biol Chem 394:1399–1410 Cascione M, De Matteis V, Toma CC, Pellegrino P, Leporatti S, Rinaldi R (2017) Morphomechanical and structural changes induced by ROCK inhibitor in breast cancer cells. Exp Cell Res 360:303–309 Chang CY, Leu JD, Lee YJ (2015) The actin depolymerizing factor (ADF)/cofilin signaling pathway and DNA damage responses in cancer. Int J Mol Sci 16:4095–4120 Charles MD, Brookfield JL, Ekwuru TC, Stockley M, Dunn J, Riddick M, Hammonds T, Trivier E, Greenland G, Wong AC, Cheasty A, Boyd S, Crighton D, Olson MF (2015) Discovery, development, and SAR of aminothiazoles as LIMK inhibitors with cellular anti-invasive properties. J Med Chem 58:8309–8313 Collazo J, Zhu B, Larkin S, Martin SK, Pu H, Horbinski C, Koochekpour S, Kyprianou N (2014) Cofilin drives cell-invasive and metastatic responses to TGF-beta in prostate cancer. Cancer Res 74:2362–2373 Desmarais V, Ghosh M, Eddy R, Condeelis J (2005) Cofilin takes the lead. J Cell Sci 118:19–26 Feng Y, Lograsso PV (2014) Rho kinase inhibitors: a patent review (2012–2013). Expert Opin Ther Pat 24:295–307 Gai WT, Yu DP, Wang XS, Wang PT (2016) Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. Oncol Lett 12:2880–2885 Goyal P, Pandey D, Siess W (2006) Phosphorylation-dependent regulation of unique nuclear and nucleolar localization signals of LIM kinase 2 in endothelial cells. J Biol Chem 281:25223–25230 Guerra FS, Oliveira RG, Fraga CAM, Mermelstein CDS, Fernandes PD (2017) ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells. Sci Rep 7:13723 Huang X, Sun D, Pan Q, Wen W, Chen Y, Xin X, Huang M, Ding J, Geng M (2014) JG6, a novel marine-derived oligosaccharide, suppresses breast cancer metastasis via binding to cofilin. Oncotarget 5:3568–3578 Jiang L, Wen J, Luo W (2015) Rhoassociated kinase inhibitor, Y27632, inhibits the invasion and proliferation of T24 and 5367 bladder cancer cells. Mol Med Rep 12:7526–7530 Johnson EO, Chang KH, Ghosh S, Venkatesh C, Giger K, Low PS, Shah K (2012) LIMK2 is a crucial regulator and effector of Aurora-A-kinase-mediated malignancy. J Cell Sci 125:1204–1216 Kalender ME, Demiryurek S, Oztuzcu S, Kizilyer A, Demiryurek AT, Sevinc A, Dikilitas M, Yildiz R, Camci C (2010) Association between the Thr431Asn polymorphism of the ROCK2 gene and risk of developing metastases of breast cancer. Oncol Res 18:583–591 Kamai T, Tsujii T, Arai K, Takagi K, Asami H, Ito Y, Oshima H (2003) Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res 9:2632–2641 Kang CG, Han HJ, Lee HJ, Kim SH, Lee EO (2015) Rho-associated kinase signaling is required for osteopontin-induced cell invasion through inactivating cofilin in human non-small cell lung cancer cell lines. Bioorg Med Chem Lett 25:1956–1960 Kapoor P, Shen X (2014) Mechanisms of nuclear actin in chromatin-remodeling complexes. Trends Cell Biol 24:238–246 Lane J, Martin TA, Watkins G, Mansel RE, Jiang WG (2008) The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. Int J Oncol 33:585–593 Li R, Doherty J, Antonipillai J, Chen S, Devlin M, Visser K, Baell J, Street I, Anderson RL, Bernard O (2013) LIM kinase inhibition reduces breast cancer growth and invasiveness but systemic inhibition does not reduce metastasis in mice. Clin Exp Metastasis 30:483–495 Li Y, Li X, Liu KR, Zhang JN, Liu Y, Zhu Y (2015) Visfatin derived from ascites promotes ovarian cancer cell migration through Rho/ROCK signaling-mediated actin polymerization. Eur J Cancer Prev 24:231–239 Liao PH, Hsu HH, Chen TS, Chen MC, Day CH, Tu CC, Lin YM, Tsai FJ, Kuo WW, Huang CY (2017) Phosphorylation of cofilin-1 by ERK confers HDAC inhibitor resistance in hepatocellular carcinoma cells via decreased ROS-mediated mitochondria injury. Oncogene 36:1978–1990 Liu X, Bi Y (2016) Y-27632 increases sensitivity of PANC-1 cells to EGCG in regulating cell proliferation and migration. Med Sci Monit 22:3529–3534 Liu S, Goldstein RH, Scepansky EM, Rosenblatt M (2009) Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res 69:8742–8751 Liu W, Zhang Q, Tang Q, Hu C, Huang J, Liu Y, Lu Y, Wang Q, Li G, Zhang R (2018) Lycorine inhibits cell proliferation and migration by inhibiting ROCK1/cofilininduced actin dynamics in HepG2 hepatoblastoma cells. Oncol Rep 40:2298–2306 Lochhead PA, Wickman G, Mezna M, Olson MF (2010) Activating ROCK1 somatic mutations in human cancer. Oncogene 29:2591–2598 Maimaiti Y, Tan J, Liu Z, Guo Y, Yan Y, Nie X, Huang B, Zhou J, Huang T (2017) Overexpression of cofilin correlates with poor survival in breast cancer: a tissue microarray analysis. Oncol Lett 14:2288–2294 Manetti F (2012) LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators. Med Res Rev 32:968–998 Mardilovich K, Baugh M, Crighton D, Kowalczyk D, Gabrielsen M, Munro J, Croft DR, Lourenco F, James D, Kalna G, Mcgarry L, Rath O, Shanks E, Garnett MJ, Mcdermott U, Brookfield J, Charles M, Hammonds T, Olson MF (2015a) LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation. Oncotarget 6:38469–38486 Mardilovich K, Gabrielsen M, Mcgarry L, Orange C, Patel R, Shanks E, Edwards J, Olson MF (2015b) Elevated LIM kinase 1 in nonmetastatic prostate cancer reflects its role in facilitating androgen receptor nuclear translocation. Mol Cancer Ther 14:246–258 Matsuoka T, Yashiro M (2014) Rho/ROCK signaling in motility and metastasis of gastric cancer. World J Gastroenterol 20:13756–13766 Meng Y, Zhang Y, Tregoubov V, Janus C, Cruz L, Jackson M, Lu WY, Macdonald JF, Wang JY, Falls DL, Jia Z (2002) Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron 35:121–133 Miyamoto C, Maehata Y, Ozawa S, Ikoma T, Kubota E, Izukuri K, Kato Y, Hata R, Lee MC (2012) Fasudil suppresses fibrosarcoma growth by stimulating secretion of the chemokine CXCL14/BRAK. J Pharmacol Sci 120:241–249 Morgan-Fisher M, Wewer UM, Yoneda A (2013) Regulation of ROCK activity in cancer. J Histochem Cytochem 61:185–198 Mu D, Zhou G, Li J, Su B, Guo H (2018) Ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated mitochondrial translocation of cofilin-1. Oncol Lett 15:3202–3206 Ohashi K, Sampei K, Nakagawa M, Uchiumi N, Amanuma T, Aiba S, Oikawa M, Mizuno K (2014) Damnacanthal, an effective inhibitor of LIM-kinase, inhibits cell migration and invasion. Mol Biol Cell 25:828–840 Park JB, Agnihotri S, Golbourn B, Bertrand KC, Luck A, Sabha N, Smith CA, Byron S, Zadeh G, Croul S, Berens M, Rutka JT (2014) Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway. Oncotarget 5:9382–9395 Philimonenko VV, Zhao J, Iben S, Dingova H, Kysela K, Kahle M, Zentgraf H, Hofmann WA, De Lanerolle P, Hozak P, Grummt I (2004) Nuclear actin and myosin I are required for RNA polymerase I transcription. Nat Cell Biol 6:1165–1172 Po’uha ST, Shum MS, Goebel A, Bernard O, Kavallaris M (2010) LIM-kinase 2, a regulator of actin dynamics, is involved in mitotic spindle integrity and sensitivity to microtubule-destabilizing drugs. Oncogene 29:597–607 Prudent R, Vassal-Stermann E, Nguyen CH, Pillet C, Martinez A, Prunier C, Barette C, Soleilhac E, Filhol O, Beghin A, Valdameri G, Honore S, Aci-Seche S, Grierson D, Antonipillai J, Li R, Di Pietro A, Dumontet C, Braguer D, Florent JC, Knapp S, Bernard O, Lafanechere L (2012) Pharmacological inhibition of LIM kinase stabilizes microtubules and inhibits neoplastic growth. Cancer Res 72:4429–4439 Prudnikova TY, Rawat SJ, Chernoff J (2015) Molecular pathways: targeting the kinase effectors of RHO-family GTPases. Clin Cancer Res 21:24–29 Prunier C, Josserand V, Vollaire J, Beerling E, Petropoulos C, Destaing O, Montemagno C, Hurbin A, Prudent R, De Koning L, Kapur R, Cohen PA, Albiges-Rizo C, Coll JL, Van Rheenen J, Billaud M, Lafanechere L (2016) LIM kinase inhibitor Pyr1 reduces the growth and metastatic load of breast cancers. Cancer Res 76:3541–3552 Prunier C, Prudent R, Kapur R, Sadoul K, Lafanechere L (2017) LIM kinases: cofilin and beyond. Oncotarget 8:41749–41763 Rak R, Haklai R, Elad-Tzfadia G, Wolfson HJ, Carmeli S, Kloog Y (2014) Novel LIMK2 inhibitor blocks Panc-1 tumor growth in a mouse xenograft model. Oncoscience 1:39–48 Rath N, Olson MF (2012) Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy. EMBO Rep 13:900–908 Sari-Hassoun M, Clement MJ, Hamdi I, Bollot G, Bauvais C, Joshi V, Toma F, Burgo A, Cailleret M, Rosales-Hernandez MC, Macias Perez ME, Chabane-Sari D, Curmi PA (2016) Cucurbitacin I elicits the formation of actin/phospho-myosin II co-aggregates by stimulation of the RhoA/ROCK pathway and inhibition of LIM-kinase. Biochem Pharmacol 102:45–63 Scott RW, Olson MF (2007) LIM kinases: function, regulation and association with human disease. J Mol Med (Berl) 85:555–568 Shoji K, Ohashi K, Sampei K, Oikawa M, Mizuno K (2012) Cytochalasin D acts as an inhibitor of the actin-cofilin interaction. Biochem Biophys Res Commun 424:52–57 Song H, Wang Y, Li L, Sui H, Wang P, Wang F (2018) Cucurbitacin E inhibits proliferation and migration of intestinal epithelial cells via activating cofilin. Front Physiol 9:1090 Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O (2005) Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J 24:473–486 Takahashi H, Koshimizu U, Miyazaki J, Nakamura T (2002) Impaired spermatogenic ability of testicular germ cells in mice deficient in the LIM-kinase 2 gene. Dev Biol 241:259–272 Takeda H, Okada M, Suzuki S, Kuramoto K, Sakaki H, Watarai H, Sanomachi T, Seino S, Yoshioka T, Kitanaka C (2016) Rho-associated protein kinase (ROCK) inhibitors inhibit survivin expression and sensitize pancreatic cancer stem cells to gemcitabine. Anticancer Res 36:6311–6318 Tang Y, He Y, Zhang P, Wang J, Fan C, Yang L, Xiong F, Zhang S, Gong Z, Nie S, Liao Q, Li X, Li X, Li Y, Li G, Zeng Z, Xiong W, Guo C (2018) LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis. Mol Cancer 17:77 Thompson JM, Nguyen QH, Singh M, Pavesic MW, Nesterenko I, Nelson LJ, Liao AC, Razorenova OV (2017) Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma. Oncogene 36:1080–1089 Van Rheenen J, Condeelis J, Glogauer M (2009) A common cofilin activity cycle in invasive tumor cells and inflammatory cells. J Cell Sci 122:305–311 Vennin C, Chin VT, Warren SC, Lucas MC, Herrmann D, Magenau A, Melenec P, Walters SN, Del Monte-Nieto G, Conway JR, Nobis M, Allam AH, Mccloy RA, Currey N, Pinese M, Boulghourjian A, Zaratzian A, Adam AA, Heu C, Nagrial AM, Chou A, Steinmann A, Drury A, Froio D, Giry-Laterriere M, Harris NL, Phan T, Jain R, Weninger W, Mcghee EJ, Whan R, Johns AL, Samra JS, Chantrill L, Gill AJ, Kohonen-Corish M, Harvey RP, Biankin AV, Australian Pancreatic Cancer Genome I, Evans TR, Anderson KI, Grey ST, Ormandy CJ, Gallego-Ortega D, Wang Y, Samuel MS, Sansom OJ, Burgess A, Cox TR, Morton JP, Pajic M, Timpson P (2017a) Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med 9:384 Vennin C, Rath N, Pajic M, Olson MF, Timpson P (2017b) Targeting ROCK activity to disrupt and prime pancreatic cancer for chemotherapy. Small GTPases 55:818–831 Vogel CJ, Smit MA, Maddalo G, Possik PA, Sparidans RW, Van Der Burg SH, Verdegaal EM, Heck AJ, Samatar AA, Beijnen JH, Altelaar AF, Peeper DS (2015) Cooperative induction of apoptosis in NRAS mutant melanoma by inhibition of MEK and ROCK. Pigment Cell Melanoma Res 28:307–317 Voorneveld PW, Kodach LL, Jacobs RJ, Liv N, Zonnevylle AC, Hoogenboom JP, Biemond I, Verspaget HW, Hommes DW, De Rooij K, Van Noesel CJ, Morreau H, Van Wezel T, Offerhaus GJ, Van Den Brink GR, Peppelenbosch MP, Ten Dijke P, Hardwick JC (2014) Loss of SMAD4 alters BMP signaling to promote colorectal cancer cell metastasis via activation of Rho and ROCK. Gastroenterology 147(196–208):e13 Wang Y, Kuramitsu Y, Kitagawa T, Baron B, Yoshino S, Maehara S, Maehara Y, Oka M, Nakamura K (2015) Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration. Cancer Lett 360:171–176 Wang ZM, Yang DS, Liu J, Liu HB, Ye M, Zhang YF (2016) ROCK inhibitor Y-27632 inhibits the growth, migration, and invasion of Tca8113 and CAL-27 cells in tongue squamous cell carcinoma. Tumour Biol 37:3757–3764 Wang H, Gu H, Feng J, Qian Y, Yang L, Jin F, Wang X, Chen J, Shi Y, Lu S, Zhao M, Liu Y (2017) Celastrus orbiculatus extract suppresses the epithelial-mesenchymal transition by mediating cytoskeleton rearrangement via inhibition of the Cofilin 1 signaling pathway in human gastric cancer. Oncol Lett 14:2926–2932 Wang W, Yang C, Nie H, Qiu X, Zhang L, Xiao Y, Zhou W, Zeng Q, Zhang X, Wu Y, Liu J, Ying M (2018) LIMK2 acts as an oncogene in bladder cancer and its functional SNP in the microRNA-135a binding site affects bladder cancer risk. Int J Cancer 144:1345–1355 Wei L, Surma M, Shi S, Lambert-Cheatham N, Shi J (2016) Novel Insights into the roles of rho kinase in cancer. Arch Immunol Ther Exp (Warsz) 64:259–278 Wioland H, Guichard B, Senju Y, Myram S, Lappalainen P, Jegou A, Romet-Lemonne G (2017) ADF/cofilin accelerates actin dynamics by severing filaments and promoting their depolymerization at both ends. Curr Biol 27(1956–1967):e7 Xia Y, Cai XY, Fan JQ, Zhang LL, Ren JH, Chen J, Li ZY, Zhang RG, Zhu F, Wu G (2015) Rho kinase inhibitor fasudil suppresses the vasculogenic mimicry of B16 mouse melanoma cells both in vitro and in vivo. Mol Cancer Ther 14:1582–1590 Xia Y, Cai X, Fan J, Zhang L, Li Z, Ren J, Wu G, Zhu F (2017) RhoA/ROCK pathway inhibition by fasudil suppresses the vasculogenic mimicry of U2OS osteosarcoma cells in vitro. Anticancer Drugs 28:514–521 Xia Y, Cai XY, Fan JQ, Zhang LL, Ren JH, Li ZY, Zhang RG, Zhu F, Wu G (2018) The role of sema4D in vasculogenic mimicry formation in non-small cell lung cancer and the underlying mechanisms. Int J Cancer 144:2227–2238 Yoshioka K, Foletta V, Bernard O, Itoh K (2003) A role for LIM kinase in cancer invasion. Proc Natl Acad Sci USA 100:7247–7252 Zhang Y, Li A, Shi J, Fang Y, Gu C, Cai J, Lin C, Zhao L, Liu S (2018a) Imbalanced LIMK1 and LIMK2 expression leads to human colorectal cancer progression and metastasis via promoting beta-catenin nuclear translocation. Cell Death Dis 9:749 Zhang Y, Wang Y, Xue J (2018b) Paclitaxel inhibits breast cancer metastasis via suppression of Aurora kinase-mediated cofilin-1 activity. Exp Ther Med 15:1269–1276 Zhao R, Choi BY, Lee MH, Bode AM, Dong Z (2016) Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer. EBioMedicine 8:30–39 Zhou Y, Su J, Shi L, Liao Q, Su Q (2013) DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway, inhibiting cell migration and invasion. Oncol Rep 29:605–612