Engine shutdown: migrastatic strategies and prevention of metastases

Trends in Cancer - Tập 9 - Trang 293-308 - 2023
Martina Raudenská1,2, Kateřina Petrláková1,2, Tamara Juriňáková1,2, Jindřiška Leischner Fialová1,2, Michaela Fojtů1,2, Milan Jakubek3, Daniel Rösel4, Jan Brábek4, Michal Masařík1,2,3
1Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00, Brno, Czech Republic
2Department of Pathological Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00 Brno, Czech Republic
3BIOCEV (Biotechnology and Biomedicine Center in Vestec), First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic
4Department of Cell Biology, BIOCEV, Faculty of Science, Charles University, CZ-252 50, Vestec, Prague-West, Czech Republic

Tài liệu tham khảo

Nguyen, 2009, Metastasis: from dissemination to organ-specific colonization, Nat. Rev. Cancer, 9, 274, 10.1038/nrc2622

Palmer, 2011, Targeting tumor cell motility to prevent metastasis, Adv. Drug Deliv. Rev., 63, 568, 10.1016/j.addr.2011.04.008

Li, 2019, On the energy efficiency of cell migration in diverse physical environments, Proc. Natl. Acad. Sci. U. S. A., 116, 23894, 10.1073/pnas.1907625116

Zhang, 2019, Energetic regulation of coordinated leader–follower dynamics during collective invasion of breast cancer cells, Proc. Natl. Acad. Sci. U. S. A., 116, 7867, 10.1073/pnas.1809964116

Zanotelli, 2019, Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making, Nat. Commun., 10, 4185, 10.1038/s41467-019-12155-z

Paul, 2017, Cancer cell motility: lessons from migration in confined spaces, Nat. Rev. Cancer, 17, 131, 10.1038/nrc.2016.123

Yamada, 2019, Mechanisms of 3D cell migration, Nat. Rev. Mol. Cell Biol., 20, 738, 10.1038/s41580-019-0172-9

Garde, 2021, Fueling cell invasion through extracellular matrix, Trends Cell Biol., 31, 445, 10.1016/j.tcb.2021.01.006

Horssen, 2008, Modulation of cell motility by spatial repositioning of enzymatic ATP/ADP exchange capacity, J. Biol. Chem., 284, 1620, 10.1074/jbc.M806974200

Papalazarou, 2020, The creatine–phosphagen system is mechanoresponsive in pancreatic adenocarcinoma and fuels invasion and metastasis, Nat. Metab., 2, 62, 10.1038/s42255-019-0159-z

Raudenska, 2019, Cisplatin enhances cell stiffness and decreases invasiveness rate in prostate cancer cells by actin accumulation, Sci. Rep., 9, 1660, 10.1038/s41598-018-38199-7

Machacek, 2009, Coordination of Rho GTPase activities during cell protrusion, Nature, 461, 99, 10.1038/nature08242

Huttenlocher, 2011, Integrins in cell migration, Cold Spring Harb. Perspect. Biol., 3, 10.1101/cshperspect.a005074

Wolf, 2013, Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force, J. Cell Biol., 201, 1069, 10.1083/jcb.201210152

Harada, 2014, Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival, J. Cell Biol., 204, 669, 10.1083/jcb.201308029

Fingleton, 2008, MMP inhibitor clinical trials – the past, present, and future, 759

Zucker, 2000, Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment, Oncogene, 19, 6642, 10.1038/sj.onc.1204097

Balzer, 2012, Physical confinement alters tumor cell adhesion and migration phenotypes, FASEB J., 26, 4045, 10.1096/fj.12-211441

Kopf, 2020, Microtubules control cellular shape and coherence in amoeboid migrating cells, J. Cell Biol., 219, 10.1083/jcb.201907154

Friedl, 2003, Tumour-cell invasion and migration: diversity and escape mechanisms, Nat. Rev. Cancer, 3, 362, 10.1038/nrc1075

Jones, 2017, Dual targeting of mesenchymal and amoeboid motility hinders metastatic behavior, Mol. Cancer Res., 15, 670, 10.1158/1541-7786.MCR-16-0411

Sahai, 2003, Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis, Nat. Cell Biol., 5, 711, 10.1038/ncb1019

Ying, 2006, The Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models, Mol. Cancer Ther., 5, 2158, 10.1158/1535-7163.MCT-05-0440

Guerra, 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, 10.1038/s41598-017-14216-z

Rath, 2017, ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth, EMBO Mol. Med., 9, 198, 10.15252/emmm.201606743

Carragher, 2006, Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function, Oncogene, 25, 5726, 10.1038/sj.onc.1209582

Chang, 2018, ROCK inhibitor enhances the growth and migration of BRAF-mutant skin melanoma cells, Cancer Sci., 109, 3428, 10.1111/cas.13786

Salhia, 2005, Inhibition of Rho-kinase affects astrocytoma morphology, motility, and invasion through activation of Rac1, Cancer Res., 65, 8792, 10.1158/0008-5472.CAN-05-0160

Stokes, 2011, Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment, Mol. Cancer Ther., 10, 2135, 10.1158/1535-7163.MCT-11-0261

Poisson, 2020, Rock inhibition promotes NaV1.5 sodium channel-dependent SW620 colon cancer cell invasiveness, Sci. Rep., 10, 13350, 10.1038/s41598-020-70378-3

Gurkar, 2013, Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress, Nat. Commun., 4, 2189, 10.1038/ncomms3189

Jing, 2020, KD025, an anti-adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2-overexpressing leukemia cells, Oncol. Lett., 20, 309-309, 10.3892/ol.2020.12172

Libanje, 2019, ROCK2 inhibition triggers the collective invasion of colorectal adenocarcinomas, EMBO J., 38, 10.15252/embj.201899299

Zeng, 2020, Rho–ROCK signaling mediates entotic cell death in tumor, Cell Death Dis., 6, 4, 10.1038/s41420-020-0238-7

Sadok, 2015, Rho kinase inhibitors block melanoma cell migration and inhibit metastasis, Cancer Res., 75, 2272, 10.1158/0008-5472.CAN-14-2156

Davies, 2009, CCT129254 (AT11854) is a well tolerated, orally bioavailable inhibitor of AKT/PKB with pharmacodynamic and antitumor activity in a range of xenograft models, Mol. Cancer Ther., 8, C208-C208, 10.1158/1535-7163.TARG-09-C208

McLeod, 2020, First-in-human study of AT13148, a dual ROCK–AKT inhibitor in patients with solid tumors, Clin. Cancer Res., 26, 4777, 10.1158/1078-0432.CCR-20-0700

Seetharaman, 2020, Cytoskeletal crosstalk in cell migration, Trends Cell Biol., 30, 720, 10.1016/j.tcb.2020.06.004

D'Amore, 2019, A journey through the cytoskeleton with protein kinase CK2, Curr. Protein Pept. Sci., 20, 547, 10.2174/1389203720666190119124846

Chua, 2017, CK2 in cancer: cellular and biochemical mechanisms and potential therapeutic target, Pharmaceuticals (Basel), 10, 18, 10.3390/ph10010018

Birus, 2022, 4,5,7-Trisubstituted indeno[1,2-b]indole inhibits CK2 activity in tumor cells equivalent to CX-4945 and shows strong anti-migratory effects, FEBS Open Bio., 12, 394, 10.1002/2211-5463.13346

Stehn, 2013, A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells, Cancer Res., 73, 5169, 10.1158/0008-5472.CAN-12-4501

Sharma, 2014, The role of Rho GTPase in cell stiffness and cisplatin resistance in ovarian cancer cells, Integr. Biol., 6, 611, 10.1039/C3IB40246K

Vassilopoulos, 2014, Synergistic therapeutic effect of cisplatin and phosphatidylinositol 3-kinase (PI3K) inhibitors in cancer growth and metastasis of Brca1 mutant tumors, J. Biol. Chem., 289, 24202, 10.1074/jbc.M114.567552

Raudenska, 2019, Unexpected therapeutic effects of cisplatin, Metallomics, 11, 1182, 10.1039/c9mt00049f

Wang, 2021, Cisplatin prevents breast cancer metastasis through blocking early EMT and retards cancer growth together with paclitaxel, Theranostics, 11, 2442, 10.7150/thno.46460

Kung, 2016, Nanoscale characterization illustrates the cisplatin-mediated biomechanical changes of B16-F10 melanoma cells, Phys. Chem. Phys., 18, 7124, 10.1039/C5CP07971C

Li, 2012, Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance, Oncogene, 31, 2412, 10.1038/onc.2011.426

Jayatilaka, 2018, EB1 and cytoplasmic dynein mediate protrusion dynamics for efficient 3-dimensional cell migration, FASEB J., 32, 1207, 10.1096/fj.201700444RR

Yang, 2010, Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs, J. Biol. Chem., 285, 32242, 10.1074/jbc.M110.160820

Čermák, 2020, Microtubule-targeting agents and their impact on cancer treatment, Eur. J. Cell Biol., 99, 10.1016/j.ejcb.2020.151075

Kamath, 2014, Mechanisms of inhibition of endothelial cell migration by taxanes, Cytoskeleton (Hoboken), 71, 46, 10.1002/cm.21153

Bonezzi, 2012, Inhibition of SIRT2 potentiates the anti-motility activity of taxanes: implications for antineoplastic combination therapies, Neoplasia (New York, N.Y.), 14, 846, 10.1593/neo.12728

Ganguly, 2015, Peloruside A is a microtubule-stabilizing agent with exceptional anti-migratory properties in human endothelial cells, Oncoscience, 2, 585, 10.18632/oncoscience.169

Kikuchi, 2008, WAVE2- and microtubule-dependent formation of long protrusions and invasion of cancer cells cultured on three-dimensional extracellular matrices, Cancer Sci., 99, 2252, 10.1111/j.1349-7006.2008.00927.x

Currier, 2017, Identification of cancer-targeted tropomyosin inhibitors and their synergy with microtubule drugs, Mol. Cancer Ther., 16, 1555, 10.1158/1535-7163.MCT-16-0873

Wang, 2020, Drug targeting the actin cytoskeleton potentiates the cytotoxicity of low dose vincristine by abrogating actin-mediated repair of spindle defects, Mol. Cancer Res., 18, 1074, 10.1158/1541-7786.MCR-19-1122

Cheng, 2021, Nano-strategies targeting the integrin αvβ3 network for cancer therapy, Cells, 10, 1684, 10.3390/cells10071684

Hao, 2021, Molybdenum dioxide (MoS2)/gadolinium (Gd) containing arginine-glycine-aspartic acid (RGD) sequences as new nano-contrast agent for cancer magnetic resonance imaging (MRI), J. Nanosci. Nanotechnol., 21, 1403, 10.1166/jnn.2021.18894

Ali, 2017, Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins, Proc. Natl. Acad. Sci., 114, E5655, 10.1073/pnas.1703151114

Wang, 2012, Assembly of aptamer switch probes and photosensitizer on gold nanorods for targeted photothermal and photodynamic cancer therapy, ACS Nano, 6, 5070, 10.1021/nn300694v

Ali, 2016, Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis, Int. J. Nanomedicine, 11, 4849, 10.2147/IJN.S109470

Ali, 2017, Nuclear membrane-targeted gold nanoparticles inhibit cancer cell migration and invasion, ACS Nano, 11, 3716, 10.1021/acsnano.6b08345

Tay, 2014, Nanoparticles strengthen intracellular tension and retard cellular migration, Nano Lett., 14, 83, 10.1021/nl4032549

Soenen, 2010, High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling, Small, 6, 832, 10.1002/smll.200902084

Roshini, 2018, pH-sensitive tangeretin-ZnO quantum dots exert apoptotic and anti-metastatic effects in metastatic lung cancer cell line, Mater. Sci. Eng. C Mater. Biol. Appl., 92, 477, 10.1016/j.msec.2018.06.073

Lyu, 2019, Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis, Signal Transduct. Target Ther., 4, 26, 10.1038/s41392-019-0054-9

Rocha, 2020, Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells, J. Nanobiotechnology, 18, 43, 10.1186/s12951-020-00604-7

Zanotelli, 2018, Regulation of ATP utilization during metastatic cell migration by collagen architecture, Mol. Biol. Cell, 29, 1, 10.1091/mbc.E17-01-0041

Mayor, 2016, The front and rear of collective cell migration, Nat. Rev. Mol. Cell Biol., 17, 97, 10.1038/nrm.2015.14

Commander, 2020, Subpopulation targeting of pyruvate dehydrogenase and GLUT1 decouples metabolic heterogeneity during collective cancer cell invasion, Nat. Commun., 11, 1533, 10.1038/s41467-020-15219-7

Tan, 2015, Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA, Cell Metab., 21, 81, 10.1016/j.cmet.2014.12.003

Bajzikova, 2019, Reactivation of dihydroorotate dehydrogenase-driven pyrimidine biosynthesis restores tumor growth of respiration-deficient cancer cells, Cell Metab., 29, 399, 10.1016/j.cmet.2018.10.014

Cunniff, 2016, AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion, Mol. Biol. Cell, 27, 2662, 10.1091/mbc.e16-05-0286

Caino, 2015, PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion, Proc. Natl. Acad. Sci. U. S. A., 112, 8638, 10.1073/pnas.1500722112

Schuler, 2017, Miro1-mediated mitochondrial positioning shapes intracellular energy gradients required for cell migration, Mol. Biol. Cell, 28, 2159, 10.1091/mbc.e16-10-0741

Caino, 2016, A neuronal network of mitochondrial dynamics regulates metastasis, Nat. Commun., 7, 13730, 10.1038/ncomms13730

Zhao, 2013, Mitochondrial dynamics regulates migration and invasion of breast cancer cells, Oncogene, 32, 4814, 10.1038/onc.2012.494

Shimada-Shimizu, 2013, Evidence that Na+/H+ exchanger 1 is an ATP-binding protein, FEBS J., 280, 1430, 10.1111/febs.12138

Drechsel, 2008, Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease, Free Radic. Biol. Med., 44, 1873, 10.1016/j.freeradbiomed.2008.02.008

Heinz, 2017, Mechanistic investigations of the mitochondrial complex I inhibitor rotenone in the context of pharmacological and safety evaluation, Sci. Rep., 7, 10.1038/srep45465

Xiao, 2020, Rotenone restrains colon cancer cell viability, motility and epithelial–mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway, Int. J. Mol. Med., 46, 700, 10.3892/ijmm.2020.4637

Jeon, 2016, Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity, Exp. Mol. Med., 48, 10.1038/emm.2016.129

Nakayama, 2016, Metformin inhibits the radiation-induced invasive phenotype of esophageal squamous cell carcinoma, Int. J. Oncol., 49, 1890, 10.3892/ijo.2016.3676

Liang, 2018, Metformin inhibited growth, invasion and metastasis of esophageal squamous cell carcinoma in vitro and in vivo, Cell. Physiol. Biochem., 51, 1276, 10.1159/000495539

Fan, 2019, Metformin suppresses the esophageal carcinogenesis in rats treated with NMBzA through inhibiting AMPK/mTOR signaling pathway, Carcinogenesis, 40, 669, 10.1093/carcin/bgy160

Liu, 2020, Metformin suppresses proliferation and invasion of drug-resistant breast cancer cells by activation of the Hippo pathway, J. Cell. Mol. Med., 24, 5786, 10.1111/jcmm.15241

Zheng, 2017, Synergistic chemopreventive and therapeutic effects of co-drug UA-Met: implication in tumor metastasis, J. Agric. Food Chem., 65, 10973, 10.1021/acs.jafc.7b04378

Jin, 2018, The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC, EBioMedicine, 37, 188, 10.1016/j.ebiom.2018.10.044

Rattan, 2011, Metformin suppresses ovarian cancer growth and metastasis with enhancement of cisplatin cytotoxicity in vivo, Neoplasia, 13, 483, 10.1593/neo.11148

Coyle, 2016, Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis, Ann. Oncol., 27, 2184, 10.1093/annonc/mdw410

Cheng, 2016, Mitochondria-targeted analogues of metformin exhibit enhanced antiproliferative and radiosensitizing effects in pancreatic cancer cells, Cancer Res., 76, 3904, 10.1158/0008-5472.CAN-15-2534

Molina, 2018, An inhibitor of oxidative phosphorylation exploits cancer vulnerability, Nat. Med., 24, 1036, 10.1038/s41591-018-0052-4

Sahlgren, 2008, Notch signaling mediates hypoxia-induced tumor cell migration and invasion, Proc. Natl. Acad. Sci., 105, 6392, 10.1073/pnas.0802047105

Ellinghaus, 2013, BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I, Cancer med., 2, 611, 10.1002/cam4.112

Bastian, 2017, AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization, Cancer Lett., 388, 149, 10.1016/j.canlet.2016.11.040

Morgan, 2015, Kalkitoxin inhibits angiogenesis, disrupts cellular hypoxic signaling, and blocks mitochondrial electron transport in tumor cells, Mar Drugs, 13, 1552, 10.3390/md13031552

Ashton, 2018, Oxidative phosphorylation as an emerging target in cancer therapy, Clin. Cancer Res., 24, 2482, 10.1158/1078-0432.CCR-17-3070

Moreira, 2006, Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure, J. Biol. Chem., 281, 10143, 10.1074/jbc.M510249200

Ma, 2015, Tamoxifen inhibits ER-negative breast cancer cell invasion and metastasis by accelerating Twist1 degradation, Int. J. Biol. Sci., 11, 618, 10.7150/ijbs.11380

Dong, 2020, Mitocans revisited: mitochondrial targeting as efficient anti-cancer therapy, Int. J. Mol. Sci., 21, 7941, 10.3390/ijms21217941

Rohlenova, 2017, Selective disruption of respiratory supercomplexes as a new strategy to suppress Her2high breast cancer, Antioxid. Redox Signal., 26, 84, 10.1089/ars.2016.6677

Krejcir, 2019, A cyclic pentamethinium salt induces cancer cell cytotoxicity through mitochondrial disintegration and metabolic collapse, Int. J. Mol. Sci., 20, 4208, 10.3390/ijms20174208

Fialova, 2022, Pentamethinium salts suppress key metastatic processes by regulating mitochondrial function and inhibiting dihydroorotate dehydrogenase respiration, Biomed. Pharmacother., 154, 10.1016/j.biopha.2022.113582

Yamaguchi, 2019, PCK1 and DHODH drive colorectal cancer liver metastatic colonization and hypoxic growth by promoting nucleotide synthesis, Elife, 8, 10.7554/eLife.52135

Grisar, 2004, Leflunomide inhibits transendothelial migration of peripheral blood mononuclear cells, Ann. Rheum. Dis., 63, 1632, 10.1136/ard.2003.018440

Quintela-Fandino, 2020, Randomized Phase 0/I trial of the mitochondrial inhibitor ME-344 or placebo added to bevacizumab in early HER2-negative Breast cancer, Clin. Cancer Res., 26, 35, 10.1158/1078-0432.CCR-19-2023

Zhang, 2019, Pharmacology of ME-344, a novel cytotoxic isoflavone, 187, 10.1016/bs.acr.2019.01.005

Modica-Napolitano, 2019, The anticancer agent elesclomol has direct effects on mitochondrial bioenergetic function in isolated mammalian mitochondria, Biomolecules, 9, 298, 10.3390/biom9080298

Blackman, 2012, Mitochondrial electron transport is the cellular target of the oncology drug elesclomol, PLoS One, 7, 10.1371/journal.pone.0029798

Sandoval-Acuña, 2021, Targeting mitochondrial iron metabolism suppresses tumor growth and metastasis by inducing mitochondrial dysfunction and mitophagy, Cancer Res., 81, 2289, 10.1158/0008-5472.CAN-20-1628

O'Day, 2013, Final results of Phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma, J. Clin. Oncol., 31, 1211, 10.1200/JCO.2012.44.5585

Ho, 2012, Importance of glycolysis and oxidative phosphorylation in advanced melanoma, Mol. Cancer, 11, 76, 10.1186/1476-4598-11-76

Yamasaki, 2011, Deferoxamine for advanced hepatocellular carcinoma, N. Engl. J. Med., 365, 576, 10.1056/NEJMc1105726

Gottwald, 2020, The iron chelator deferasirox causes severe mitochondrial swelling without depolarization due to a specific effect on inner membrane permeability, Sci. Rep., 10, 1577, 10.1038/s41598-020-58386-9

Lui, 2013, The iron chelator, deferasirox, as a novel strategy for cancer treatment: oral activity against human lung tumor xenografts and molecular mechanism of action, Mol. Pharmacol., 83, 179, 10.1124/mol.112.081893

Fryknäs, 2016, Iron chelators target both proliferating and quiescent cancer cells, Sci. Rep., 6, 38343, 10.1038/srep38343

Hooda, 2013, Enhanced heme function and mitochondrial respiration promote the progression of lung cancer cells, PLoS One, 8, 10.1371/journal.pone.0063402

Kalainayakan, 2019, Cyclopamine tartrate, a modulator of hedgehog signaling and mitochondrial respiration, effectively arrests lung tumor growth and progression, Sci. Rep., 9, 1405, 10.1038/s41598-018-38345-1

Marlein, 2019, CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma, Cancer Res., 79, 2285, 10.1158/0008-5472.CAN-18-0773

Sahu, 2018, Tunneling nanotubes: a versatile target for cancer therapy, Curr. Cancer Drug Targets, 18, 514, 10.2174/1568009618666171129222637

Desgrosellier, 2010, Integrins in cancer: biological implications and therapeutic opportunities, Nat. Rev. Cancer, 10, 9, 10.1038/nrc2748

Veevers-Lowe, 2011, Mesenchymal stem cell migration is regulated by fibronectin through α5β1-integrin-mediated activation of PDGFR-β and potentiation of growth factor signals, J. Cell Sci., 124, 1288, 10.1242/jcs.076935

Cianfrocca, 2006, Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2), a beta integrin antagonist, in patients with solid tumours, Br. J. Cancer, 94, 1621, 10.1038/sj.bjc.6603171

Infante, 2012, Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors, J. Clin. Oncol., 30, 1527, 10.1200/JCO.2011.38.9346

Dawson, 2021, Targeting FAK in anticancer combination therapies, Nat. Rev. Cancer, 21, 313, 10.1038/s41568-021-00340-6

Mak, 2019, A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours, Br. J. Cancer, 120, 975, 10.1038/s41416-019-0452-3

Grimes, 2021, The R-enantiomer of ketorolac reduces ovarian cancer tumor burden in vivo, BMC Cancer, 21, 40, 10.1186/s12885-020-07716-1

Hsu, 2018, NVP-BEZ235 attenuated cell proliferation and migration in the squamous cell carcinoma of oral cavities and p70S6K inhibition mimics its effect, Int. J. Mol. Sci., 19, 3546, 10.3390/ijms19113546

Rispal, 2015, Target of rapamycin complex 2 regulates actin polarization and endocytosis via multiple pathways, J. Biol. Chem., 290, 14963, 10.1074/jbc.M114.627794

Bonelli, 2015, Inhibition of PI3K pathway reduces invasiveness and epithelial-to-mesenchymal transition in squamous lung cancer cell lines harboring PIK3CA gene alterations, Mol. Cancer Ther., 14, 1916, 10.1158/1535-7163.MCT-14-0892

Nakashima, 1998, Combination therapy of fasudil hydrochloride and ozagrel sodium for cerebral vasospasm following aneurysmal subarachnoid hemorrhage, Neurol. Med. Chir. (Tokyo), 38, 805, 10.2176/nmc.38.805

Teiti, 2015, In vivo effects in melanoma of ROCK inhibition-induced FasL overexpression, Front. Oncol., 5, 156, 10.3389/fonc.2015.00156

Patel, 2012, RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer, Cancer Res., 72, 5025, 10.1158/0008-5472.CAN-12-0954

Borad, 2021, Silmitasertib (CX-4945) in combination with gemcitabine and cisplatin as first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma: a phase Ib/II study, J. Clin. Oncol., 39, 312, 10.1200/JCO.2021.39.3_suppl.312

Stemberkova-Hubackova, 2022, Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy, Clin. Transl. Med., 12, 10.1002/ctm2.645

Hayat, 2022, Feasibility and safety of targeting mitochondria for cancer therapy – preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor, Cancer Biol. Ther., 23, 117, 10.1080/15384047.2022.2029132

Hsieh, 2019, Miro1 marks Parkinson’s disease subset and Miro1 reducer rescues neuron loss in Parkinson’s models, Cell Metab., 30, 1131, 10.1016/j.cmet.2019.08.023