Abstract
Majority of the deaths associated with cancer are attributed to metastasis. Till now there had been no cure of metastasis. Metastatic cells are usually resistant to conventional radiotherapy and chemotherapeutic agents. Metastasis can occur even after decades of treatment of primary tumor. Insights into the molecular mechanisms promoting metastasis could help in developing novel techniques that will prevent development of metastasis. The chapter discusses the major molecular mechanisms that support metastasis. It highlights the mechanisms involved in metastatic dormancy, immunomodulation, and mechano-transduction and their possible role in establishment of metastasis. It gives in-depth review of tumor microenvironment and how microenvironment plays role in supporting micrometastasis. It also discusses the mechanisms and factors which help the micrometastasis to escape the immune response and develop overt metastasis.
Keywords
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Patel P, Chen EI (2012) Cancer stem cells, tumor dormancy, and metastasis. Front Endocrinol 3:125
Smith BN, Bhowmick NA (2016) Role of EMT in metastasis and therapy resistance. J Clin Med 5(2):E17
Chaffer CL, San Juan BP, Lim E, Weinberg RA (2016) EMT, cell plasticity and metastasis. Cancer Metastasis Rev 35(4):645–654
Jablonska-Trypuc A, Matejczyk M, Rosochacki S (2016) Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem 31(suppl 1):177–183
Jiang WG, Sanders AJ, Katoh M, Ungefroren H, Gieseler F, Prince M et al (2015) Tissue invasion and metastasis: molecular, biological and clinical perspectives. Semin Cancer Biol 35(Suppl):S244–SS75
Lambert AW, Pattabiraman DR, Weinberg RA (2017) Emerging biological principles of metastasis. Cell 168(4):670–691
Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7(11):834–846
Lipworth S, Hammond RJ, Baron VO, Hu Y, Coates A, Gillespie SH (2016) Defining dormancy in mycobacterial disease. Tuberculosis 99:131–142
Sosa MS, Bragado P, Aguirre-Ghiso JA (2014) Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer 14(9):611–622
Manjili MH (2017) Tumor dormancy and relapse: from a natural byproduct of evolution to a disease state. Cancer Res 77(10):2564–2569
Hadfield G (1954) The dormant cancer cell. Br Med J 2(4888):607–610
Hosseini H, Obradovic MMS, Hoffmann M, Harper KL, Sosa MS, Werner-Klein M et al (2016) Early dissemination seeds metastasis in breast cancer. Nature 540(7634):552–558
Gao XL, Zhang M, Tang YL, Liang XH (2017) Cancer cell dormancy: mechanisms and implications of cancer recurrence and metastasis. Onco Targets Ther 10:5219–5228
Gomis RR, Gawrzak S (2017) Tumor cell dormancy. Mol Oncol 11(1):62–78
Aguirre-Ghiso JA, Estrada Y, Liu D, Ossowski L (2003) ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res 63(7):1684–1695
Gay LJ, Malanchi I (2017) The sleeping ugly: tumour microenvironment’s act to make or break the spell of dormancy. Biochim Biophys Acta Rev Cancer 1868(1):231–238
Sosa MS, Avivar-Valderas A, Bragado P, Wen HC, Aguirre-Ghiso JA (2011) ERK1/2 and p38alpha/beta signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clin Cancer Res 17(18):5850–5857
Jo H, Jia Y, Subramanian KK, Hattori H, Luo HR (2008) Cancer cell-derived clusterin modulates the phosphatidylinositol 3′-kinase-Akt pathway through attenuation of insulin-like growth factor 1 during serum deprivation. Mol Cell Biol 28(13):4285–4299
Vera-Ramirez L (2019) Cell-intrinsic survival signals. The role of autophagy in metastatic dissemination and tumor cell dormancy. Semin Cancer Biol. https://doi.org/10.1016/j.semcancer.2019.07.027. [Epub ahead of print]
Prunier C, Baker D, ten Dijke P, Ritsma L (2019) TGF-β family signaling pathways in cellular dormancy. Trends Cancer 5(1):66–78
Kobayashi A, Okuda H, Xing F, Pandey PR, Watabe M, Hirota S et al (2011) Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med 208(13):2641–2655
Seidi K, Manjili MH, Jahanban-Esfahlan R, Javaheri T (2018) Tumor cell dormancy: threat or opportunity in the fight against cancer. Cancer 11(8):1207
Wang H-F, Wang S-S, Huang M-C, Liang X-H, Tang Y-J, Tang Y-L (2019) Targeting immune-mediated dormancy: a promising treatment of cancer. Front Oncol 9:498
Osisami M, Keller ET (2013) Mechanisms of metastatic tumor dormancy. J Clin Med 2(3):136–150
Saudemont A, Hamrouni A, Marchetti P, Liu J, Jouy N, Hetuin D et al (2007) Dormant tumor cells develop cross-resistance to apoptosis induced by CTLs or imatinib mesylate via methylation of suppressor of cytokine signaling 1. Cancer Res 67(9):4491–4498
Zhou Y, Su Y, Zhu H, Wang X, Li X, Dai C et al (2019) Interleukin-23 receptor signaling mediates cancer dormancy and radioresistance in human esophageal squamous carcinoma cells via the Wnt/Notch pathway. J Mol Med 97(2):177–188
Yadav AS, Pandey PR, Butti R, Radharani NNV, Roy S, Bhalara SR et al (2018) The biology and therapeutic implications of tumor dormancy and reactivation. Front Oncol 8:72
Senft D, Ze Ronai A (2016) Immunogenic, cellular, and angiogenic drivers of tumor dormancy-a melanoma view. Pigment Cell Melanoma Res 29(1):27–42
Straume O, Shimamura T, Lampa MJ, Carretero J, Oyan AM, Jia D et al (2012) Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer. Proc Natl Acad Sci U S A 109(22):8699–8704
Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H et al (2013) The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 15(7):807–817
Hofstetter CP, Burkhardt JK, Shin BJ, Gursel DB, Mubita L, Gorrepati R et al (2012) Protein phosphatase 2A mediates dormancy of glioblastoma multiforme-derived tumor stem-like cells during hypoxia. PLoS One 7(1):e30059
Weidenfeld K, Schif-Zuck S, Abu-Tayeh H, Kang K, Kessler O, Weissmann M et al (2016) Dormant tumor cells expressing LOXL2 acquire a stem-like phenotype mediating their transition to proliferative growth. Oncotarget 7(44):71362–71377
Endo H, Inoue M (2019) Dormancy in cancer. Cancer Sci 110(2):474–480
Alison MR, Islam S, Wright NA (2010) Stem cells in cancer: instigators and propagators? J Cell Sci 123(Pt 14):2357–2368
Chaffer CL, Brueckmann I, Scheel C, Kaestli AJ, Wiggins PA, Rodrigues LO et al (2011) Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci U S A 108(19):7950–7955
Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M et al (2007) The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 9(2):218–224
Sinha G, Sherman LS, Sandiford OA, Williams LM, Ayer S, Walker ND et al (2016) Mesenchymal stem cell-breast cancer stem cell: relevance to dormancy. J Cancer Stem Cell Res 4:1
Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9(4):285–293
Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G et al (2017) Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer 17(5):302–317
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827
Liu Y, Cao X (2016) Characteristics and Significance of the pre-metastatic Niche. Cancer Cell 30(5):668–681
Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK et al (2015) Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 17(6):816–826
Guise T (2010) Examining the metastatic niche: targeting the microenvironment. Semin Oncol 37(Suppl 2):S2–S14
Gupta GP, Nguyen DX, Chiang AC, Bos PD, Kim JY, Nadal C et al (2007) Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446(7137):765–770
Hiratsuka S, Goel S, Kamoun WS, Maru Y, Fukumura D, Duda DG et al (2011) Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation. Proc Natl Acad Sci U S A 108(9):3725–3730
Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR et al (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475(7355):222–225
Labelle M, Begum S, Hynes RO (2014) Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci U S A 111(30):E3053–E3061
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M et al (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527(7578):329–335
Lukanidin E, Sleeman JP (2012) Building the niche: the role of the S100 proteins in metastatic growth. Semin Cancer Biol 22(3):216–225
Lu X, Kang Y (2007) Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia 12(2-3):153–162
Sharma SK, Chintala NK, Vadrevu SK, Patel J, Karbowniczek M, Markiewski MM (2015) Pulmonary alveolar macrophages contribute to the premetastatic niche by suppressing antitumor T cell responses in the lungs. J Immunol 194(11):5529–5538
Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF et al (2011) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481(7379):85–89
Deng X, Ao S, Hou J, Li Z, Lei Y, Lyu G (2019) Prognostic significance of periostin in colorectal cancer. Chin J Cancer Res 31(3):547–556
Kudo A (2011) Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell. Cell Mol Life Sci 68(19):3201–3207
Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y et al (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457(7225):102–106
Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A et al (2009) Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15(1):35–44
Xiong A, Liu Y (2017) Targeting hypoxia inducible factors-1α as a novel therapy in fibrosis. Front Pharmacol 8:326
Cox TR, Bird D, Baker AM, Barker HE, Ho MW, Lang G et al (2013) LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res 73(6):1721–1732
Ahn GO, Brown JM (2008) Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. Cancer Cell 13(3):193–205
Casbon A-J, Reynaud D, Park C, Khuc E, Gan DD, Schepers K et al (2015) Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc Natl Acad Sci U S A 112(6):E56–E75
Wu CF, Andzinski L, Kasnitz N, Kroger A, Klawonn F, Lienenklaus S et al (2015) The lack of type I interferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung. Int J Cancer 137(4):837–847
Wculek SK, Malanchi I (2015) Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature 528(7582):413–417
Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ et al (2014) Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 156(5):1002–1016
Massague J, Obenauf AC (2016) Metastatic colonization by circulating tumour cells. Nature 529(7586):298–306
Oh M, Nor JE (2015) The perivascular niche and self-renewal of stem cells. Front Physiol 6:367
Ding L, Saunders TL, Enikolopov G, Morrison SJ (2012) Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481(7382):457–462
Celia-Terrassa T, Kang Y (2018) Metastatic niche functions and therapeutic opportunities. Nat Cell Biol 20(8):868–877
Borovski T, De Sousa EMF, Vermeulen L, Medema JP (2011) Cancer stem cell niche: the place to be. Cancer Res 71(3):634–639
Doherty MJ, Ashton BA, Walsh S, Beresford JN, Grant ME, Canfield AE (1998) Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res 13(5):828–838
Plaks V, Kong N, Werb Z (2015) The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell 16(3):225–238
Ting Koh Y, Luz García-Hernández M, Martin Kast W (2006) Tumor immune escape mechanisms. In: Teicher BA (ed) Cancer drug resistance. Humana Press, Totowa, pp 577–602
Johansen LL, Lock-Andersen J, Hviid TVF (2016) The pathophysiological impact of HLA class Ia and HLA-G expression and regulatory T cells in malignant melanoma: a review. J Immunol Res 2016:6829283
Fiore E, Fusco C, Romero P, Stamenkovic I (2002) Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity. Oncogene 21(34):5213–5223
Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800
Choi IH, Zhu G, Sica GL, Strome SE, Cheville JC, Lau JS et al (2003) Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol 171(9):4650–4654
Garg AD, Coulie PG, Van den Eynde BJ, Agostinis P (2017) Integrating next-generation dendritic cell vaccines into the current cancer immunotherapy landscape. Trends Immunol 38(8):577–593
Loro LL, Ohlsson M, Vintermyr OK, Liavaag PG, Jonsson R, Johannessen AC (2001) Maintained CD40 and loss of polarised CD40 ligand expression in oral squamous cell carcinoma. Anticancer Res 21(1a):113–117
Disis ML (2010) Immune regulation of cancer. J Clin Oncol 28(29):4531–4538
Gonzalez H, Hagerling C, Werb Z (2018) Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev 32(19-20):1267–1284
Albini A, Bruno A, Noonan DM, Mortara L (2018) Contribution to tumor angiogenesis from innate immune cells within the tumor microenvironment: implications for immunotherapy. Front Immunol 9:527
Multhoff G, Molls M, Radons J (2011) Chronic inflammation in cancer development. Front Immunol 2:98
Yan C, Theodorescu D (2018) RAL GTPases: biology and potential as therapeutic targets in cancer. Pharmacol Rev 70(1):1–11
Liu T, Zhang L, Joo D, Sun S-C (2017) NF-κB signaling in inflammation. Signal Transduct Target Ther 2:17023
Liu J, Lin PC, Zhou BP (2015) Inflammation fuels tumor progress and metastasis. Curr Pharm Des 21(21):3032–3040
Rivera-Cruz CM, Shearer JJ, Figueiredo Neto M, Figueiredo ML (2017) The immunomodulatory effects of mesenchymal stem cell polarization within the tumor microenvironment niche. Stem Cells Int 2017:4015039
Bouchlaka MN, Hematti P, Capitini CM (2017) Therapeutic purposes and risks of ex vivo expanded mesenchymal stem/stromal cells. In: Mesenchymal stromal cells as tumor stromal modulators. Elsevier, Amsterdam
Ribeiro A, Laranjeira P, Mendes S, Velada I, Leite C, Andrade P et al (2013) Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther 4(5):125
Liu WH, Liu JJ, Wu J, Zhang LL, Liu F, Yin L et al (2018) Retraction: novel mechanism of inhibition of dendritic cells maturation by mesenchymal stem cells via interleukin-10 and the JAK1/STAT3 signaling pathway. PLoS One 13(3):e0194455
Zhao ZG, Xu W, Sun L, Li WM, Li QB, Zou P (2012) The characteristics and immunoregulatory functions of regulatory dendritic cells induced by mesenchymal stem cells derived from bone marrow of patient with chronic myeloid leukaemia. Eur J Cancer 48(12):1884–1895
Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298(Pt 2):249–258
Choudhari SK, Chaudhary M, Bagde S, Gadbail AR, Joshi V (2013) Nitric oxide and cancer: a review. World J Surg Oncol 11:118
Eyler CE, Wu Q, Yan K, MacSwords JM, Chandler-Militello D, Misuraca KL et al (2011) Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2. Cell 146(1):53–66
Lu G, Zhang R, Geng S, Peng L, Jayaraman P, Chen C et al (2015) Myeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization. Nat Commun 6:6676
Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D et al (2011) Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med 208(10):1949–1962
Gehad AE, Lichtman MK, Schmults CD, Teague JE, Calarese AW, Jiang Y et al (2012) Nitric oxide-producing myeloid-derived suppressor cells inhibit vascular E-selectin expression in human squamous cell carcinomas. J Invest Dermatol 132(11):2642–2651
Douguet L, Bod L, Lengagne R, Labarthe L, Kato M, Avril MF et al (2016) Nitric oxide synthase 2 is involved in the pro-tumorigenic potential of gammadelta17 T cells in melanoma. Oncoimmunology 5(8):e1208878
Salimian Rizi B, Achreja A, Nagrath D (2017) Nitric oxide: the forgotten child of tumor metabolism. Trends Cancer 3(9):659–672
Huber V, Camisaschi C, Berzi A, Ferro S, Lugini L, Triulzi T et al (2017) Cancer acidity: an ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin Cancer Biol 43:74–89
Nakagawa Y, Negishi Y, Shimizu M, Takahashi M, Ichikawa M, Takahashi H (2015) Effects of extracellular pH and hypoxia on the function and development of antigen-specific cytotoxic T lymphocytes. Immunol Lett 167(2):72–86
Lotzova E, Savary CA, Herberman RB (1987) Induction of NK cell activity against fresh human leukemia in culture with interleukin 2. J Immunol 138(8):2718–2727
Rocca YS, Roberti MP, Arriaga JM, Amat M, Bruno L, Pampena MB et al (2013) Altered phenotype in peripheral blood and tumor-associated NK cells from colorectal cancer patients. Innate Immun 19(1):76–85
Dong H, Bullock TN (2014) Metabolic influences that regulate dendritic cell function in tumors. Front Immunol 5:24
Cao TM, Takatani T, King MR (2013) Effect of extracellular pH on selectin adhesion: theory and experiment. Biophys J 104(2):292–299
Bellocq A, Suberville S, Philippe C, Bertrand F, Perez J, Fouqueray B et al (1998) Low environmental pH is responsible for the induction of nitric-oxide synthase in macrophages. Evidence for involvement of nuclear factor-kappa B activation. J Biol Chem 273(9):5086–5092
Kinoshita H, Yashiro M, Fukuoka T, Hasegawa T, Morisaki T, Kasashima H et al (2015) Diffuse-type gastric cancer cells switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis in hypoxic tumor microenvironments. Carcinogenesis 36(12):1511–1520
Ohue Y, Nishikawa H (2019) Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? Cancer Sci 110(7):2080–2089
Wei SC, Yang J (2016) Forcing through tumor metastasis: the interplay between tissue rigidity and epithelial-mesenchymal transition. Trends Cell Biol 26(2):111–120
El-Haibi CP, Bell GW, Zhang J, Collmann AY, Wood D, Scherber CM et al (2012) Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Proc Natl Acad Sci U S A 109(43):17460–17465
Riaz M, Sieuwerts AM, Look MP, Timmermans MA, Smid M, Foekens JA et al (2012) High TWIST1 mRNA expression is associated with poor prognosis in lymph node-negative and estrogen receptor-positive human breast cancer and is co-expressed with stromal as well as ECM related genes. Breast Cancer Res 14(5):R123
Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI et al (2013) Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol 15(6):637–646
Hebner C, Weaver VM, Debnath J (2008) Modeling morphogenesis and oncogenesis in three-dimensional breast epithelial cultures. Annu Rev Pathol 3:313–339
Northcott JM, Dean IS, Mouw JK, Weaver VM (2018) Feeling stress: the mechanics of cancer progression and aggression. Front Cell Dev Biol 6:17
Broders-Bondon F, Nguyen Ho-Bouldoires TH, Fernandez-Sanchez ME, Farge E (2018) Mechanotransduction in tumor progression: the dark side of the force. J Cell Biol 217(5):1571–1587
DuFort CC, Paszek MJ, Weaver VM (2011) Balancing forces: architectural control of mechanotransduction. Nat Rev Mol Cell Biol 12(5):308–319
Kou C-TJ, Kandpal RP (2018) Differential expression patterns of Eph receptors and ephrin ligands in human cancers. Biomed Res Int 2018:23
Ehrlicher AJ, Nakamura F, Hartwig JH, Weitz DA, Stossel TP (2011) Mechanical strain in actin networks regulates FilGAP and integrin binding to filamin A. Nature 478(7368):260–263
Iwamoto DV, Calderwood DA (2015) Regulation of integrin-mediated adhesions. Curr Opin Cell Biol 36:41–47
Zhang K, Corsa CA, Ponik SM, Prior JL, Piwnica-Worms D, Eliceiri KW et al (2013) The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nat Cell Biol 15(6):677–687
Tsai JH, Yang J (2013) Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev 27(20):2192–2206
Scott LE, Weinberg SH, Lemmon CA (2019) Mechanochemical signaling of the extracellular matrix in epithelial-mesenchymal transition. Front Cell Dev Biol 7:135
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C et al (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939
Scarpa E, Szabo A, Bibonne A, Theveneau E, Parsons M, Mayor R (2015) Cadherin switch during EMT in neural crest cells leads to contact inhibition of locomotion via repolarization of forces. Dev Cell 34(4):421–434
Basu S, Cheriyamundath S, Ben-Ze’ev A (2018) Cell-cell adhesion: linking Wnt/β-catenin signaling with partial EMT and stemness traits in tumorigenesis. F1000Res 7:488
Gomez EW, Chen QK, Gjorevski N, Nelson CM (2010) Tissue geometry patterns epithelial-mesenchymal transition via intercellular mechanotransduction. J Cell Biochem 110(1):44–51
Zanetti D, Llenbach R, Plodinec M, Oertle P, Redling K et al (2018) Length scale matters: real-time elastography versus nanomechanical profiling by atomic force microscopy for the diagnosis of breast lesions. Biomed Res Int 2018:12
Lopez JI, Kang I, You WK, McDonald DM, Weaver VM (2011) In situ force mapping of mammary gland transformation. Integr Biol 3(9):910–921
Affo S, Yu LX, Schwabe RF (2017) The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu Rev Pathol 12:153–186
Panera N, Crudele A, Romito I, Gnani D, Alisi A (2017) Focal adhesion kinase: insight into molecular roles and functions in hepatocellular carcinoma. Int J Mol Sci 18(1):99
Celià-Terrassa T, Kang Y (2016) Distinctive properties of metastasis-initiating cells. Genes Dev 30(8):892–908
Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147(2):275–292
Cooper J, Giancotti FG (2019) Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell 35(3):347–367
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Riaz, R., Abbas, S.R., Shabbir, M. (2020). Adapting the Foreign Soil: Factors Promoting Tumor Metastasis. In: Masood, N., Shakil Malik, S. (eds) 'Essentials of Cancer Genomic, Computational Approaches and Precision Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-15-1067-0_8
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