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Differential Effect of the Focal Adhesion Kinase Y397F Mutant on v-Src-Stimulated Cell Invasion and Tumor Growth

  • Published:
Journal of Biomedical Science

Summary

Upon cell adhesion to extracellular matrix proteins, focal adhesion kinase (FAK) rapidly undergoes autophosphorylation on its Tyr-397 which consequently serves as a binding site for the Src homology 2 domains of the Src family protein kinases and several other intracellular signaling molecules. In this study, we have attempted to examine the effect of the FAK Y397F mutant on v-Src-stimulated cell transformation by establishing an inducible expression of the Y397F mutant in v-Src-transformed FAK-null (FAK−/−) mouse embryo fibroblasts. We found that the FAK Y397F mutant had both positive and negative effects on v-Src-stimulated cell transformation; it promoted v-Src-stimulated invasion, but on the other hand it inhibited the v-Src-stimulated anchorage-independent cell growth in vitro and tumor formation in vivo . The positive effect of the Y397F mutant on v-Src-stimulated invasion was correlated with an increased expression of matrix metalloproteinase-2, both of which were inhibited by the specific phosphatidylinositol 3-kinase inhibitor wortmannin or a dominant negative mutant of AKT, suggesting a critical role for the phosphatidylinositol 3-kinase/AKT pathway in both events. However, the expression of the Y397F mutant rendered v-Src-transformed FAK−/− cells susceptible to anoikis, correlated with suppression on v-Src-stimulated activation of ERK and AKT. In addition, under anoikis stress, the induction of the Y397F mutant in v-Src-transformed FAK−/− cells selectively led to a decrease in the level of p130Cas, but not other focal adhesion proteins such as talin, vinculin, and paxillin. These results suggest that FAK may increase the susceptibility of v-Src-transformed cells to anoikis by modulating the level of p130Cas.

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Abbreviations

Cas:

Crk-associated substrate

ERK:

extracellular signal-regulated kinase

FAK:

focal adhesion kianse

HA:

hemagglutinin

IB:

immunoblotting

IP:

immunoprecipitation

JNK:

c-Jun N-terminal kinase

MMP:

matrix metalloproteinase

PI3K:

phosphatidylinositol 3-kinase

SH:

Src homology

Src:

sarcoma

STAT3:

signal transducers and activators of transcription 3

Tet:

tetracycline

Tyr:

tyrosine

v-Scr:

viral Scr

Wt:

wild type

References

  1. Stehelin, D., Varmus, H.E., Bishop, J.M., Vogt, P.K. (1976) "DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA" Nature 260: 170-173

    Article  PubMed  CAS  Google Scholar 

  2. Shalloway, D., Zelenetz, A.D., Cooper, G.M. (1981) "Molecular cloning and characterization of the chicken gene homologous to the transforming gene of Rous sarcoma virus" Cell 24: 531-541

    Article  PubMed  CAS  Google Scholar 

  3. Parker, R.C., Varmus, H.E., Bishop, J.M. (1984) "Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src" Cell 37: 131-139

    Article  PubMed  CAS  Google Scholar 

  4. Thomas, S.M., Brugge, J.S. (1997) "Cellular functions regulated by Src family kinases" Annu. Rev. Cell Dev. Biol. 13: 513-609

    Article  PubMed  CAS  Google Scholar 

  5. Wyke, A.W., Frame, M.C., Gillespie, D.A., Chudleigh, A., Wyke, J.A. (1995) "Mitogenesis by v-Src: fluctuations throughout G1 of classical immediate early AP-1 and mitogen-activated protein kinase responses that parallel the need for the oncoprotein" Cell Growth Differ. 6: 1225-1234

    PubMed  CAS  Google Scholar 

  6. Johnson, D., Agochiya, M., Samejima, K., Earnshaw, W., Frame, M., Wyke, J. (2000) "Regulation of both apoptosis and cell survival by the v-Src oncoprotein" Cell Growth Differ. 7: 685-696

    Article  CAS  Google Scholar 

  7. Bowman, T., Broome, M.A., Sinibaldi, D., Wharton, W., Pledger, W.J., Sedivy, J.M., Irby, R., Yeatman, T., Courtneidge, S.A., Jove, R. (2001) "Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis" Proc. Natl. Acad. Sci. USA 98: 7319-7324

    Article  PubMed  CAS  Google Scholar 

  8. Frame, M.C. (2002) "Src in cancer: deregulation and consequences for cell behaviour" Biochim. Biophys. Acta 1602: 114-130

    PubMed  CAS  Google Scholar 

  9. Schaller, M.D., Borgman, C.A., Cobb, B.S., Vines, R.R., Reynolds, A.B., Parsons, J.T. (1992) "pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions" Proc. Natl. Acad. Sci. USA 89: 5192-5196

    Article  PubMed  CAS  Google Scholar 

  10. Hanks, S.K., Calalb, M.B., Harper, M.C., Patel, S.K. (1992) "Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin" Proc. Natl. Acad. Sci. USA 89: 8487-8491

    Article  PubMed  CAS  Google Scholar 

  11. Richardson, A., Malik, R.K., Hildebrand, J.D., Parsons, J.T. (1997) "Inhibition of cell spreading by expression of the C-terminal domain of focal adhesion kinase (FAK) is rescued by coexpression of Src or catalytically inactive FAK: a role for paxillin tyrosine phosphorylation" Mol. Cell. Biol. 17: 6906-6914

    PubMed  CAS  Google Scholar 

  12. Ilic, D., Furuta, Y., Kanazawa, S., Takeda, N., Sobue, K., Nakatsuji, N., Nomura, S., Fujimoto, J., Okada, M., Yamamoto, T., Aizawa, S. (1995) "Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice" Nature 377: 539-544

    Article  PubMed  CAS  Google Scholar 

  13. Cary, L.A., Chang, J.F., Guan, J.L. (1996) "Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn" J. Cell Sci. 109: 1787-1794

    PubMed  CAS  Google Scholar 

  14. Zhao, J.H., Reiske, H., Guan, J.L. (1998) "Regulation of the cell cycle by focal adhesion kinase" J. Cell Biol. 143: 1997-2008

    Article  PubMed  CAS  Google Scholar 

  15. Oktay, M., Wary, K.K., Dans, M., Rirge, R.B., Giancotti, F.G. (1999) "Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH2-terminal kinase and progression through the G1 phase of the cell cycle" J. Cell Biol. 145: 1461-1469

    Article  PubMed  CAS  Google Scholar 

  16. Frisch, S.M., Vuori, K., Ruoslahti, E., Chan-Hui, P.Y. (1996) "Control of adhesion-dependent cell survival by focal adhesion kinase" J. Cell Biol. 134: 793-799

    Article  PubMed  CAS  Google Scholar 

  17. Ilic, D., Almeida, E.A.C., Schlaepfer, D.D., Dazin, P., Aizawa, S., Damsky, C.H. (1998) "Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis" J. Cell Biol. 143: 547-560

    Article  PubMed  CAS  Google Scholar 

  18. Chan, P.C., Lai, J.F., Cheng, C.H., Tang, M.J., Chiu, C.C., Chen, H.C. (1999) "Suppression of ultraviolet irradiation- induced apoptosis by overexpression of focal adhesion kinase in Madin–Darby canine kidney cells" J. Biol. Chem. 274: 26901-26906

    Article  PubMed  CAS  Google Scholar 

  19. Almeida, E.A.C., Ilic, D., Han, Q., Hauck, C.R., Jin, F., Kawakatsu, H., Schlaepfer, D.D., Damsky, C.H. (2000) "Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase" J. Cell Biol. 149: 741-754

    Article  PubMed  CAS  Google Scholar 

  20. Rankin, S., Rozengurt, E. (1994) "Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and paxillin tyrosine phosphorylation in Swiss 3T3 cells. Bell-shaped dose response and cross-talk with bombesin" J. Biol. Chem. 269: 704-710

    PubMed  CAS  Google Scholar 

  21. Hatai, M., Hashi, H., Mogi, A., Soga, H., Yokota, J., Yaoi, Y. (1994) "Stimulation of tyrosine- and serine-phosphorylation of focal adhesion kinase in mouse 3T3 cells by fibronectin and fibroblast growth factor" FEBS Lett. 350: 113-116

    Article  PubMed  CAS  Google Scholar 

  22. Chen, H.C., Chan, P.C., Tang, M.J., Cheng, C.H., Chang, T.J. (1998) "Tyrosine phosphorylation of focal adhesion kinase stimulated by hepatocyte growth factor leads to mitogen-activated protein kinase activation" J. Biol. Chem. 273: 25777-25782

    Article  PubMed  CAS  Google Scholar 

  23. Sieg, D.J., Hauck, C.R., Ilic, D., Klingbell, C.K., Schaefer, E., Damsky, C.H., Schlaepfer, D.D. (2000) "FAK integrates growth-factor and integrin signals to promote cell migration" Nat. Cell Biol. 2: 249-256

    Article  PubMed  CAS  Google Scholar 

  24. Weiner, T.M., Liu, E.T., Craven, R.J., Cance, W.G. (1993) "Expression of focal adhesion kinase gene and invasive cancer" Lancet 342: 1024-1025

    Article  PubMed  CAS  Google Scholar 

  25. Owens, L.V., Xu, L., Craven, R.J., Dent, G.A., Weiner, T.M., Knornberg, L., Liu, E.T., Cance, W.G. (1995) "Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors" Cancer Res. 55: 2752-2755

    PubMed  CAS  Google Scholar 

  26. Agochiya, M., Brunton, V.G., Owen, D.W., Parkinson, E.K., Paraskeva, C., Keith, W.N., Frame, M.C. (2000) "Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells" Oncogene 18: 5646-5653

    Article  CAS  Google Scholar 

  27. Oktay, M.H., Oktay, K., Hamele-Bena, D., Buyuk, A., Koss, L.G. (2003) "Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas" Hum. Pathol. 34: 240-245

    Article  PubMed  CAS  Google Scholar 

  28. Cobb, B.S., Schaller, M.D., Leu, T.H., Parsons, J.T. (1994) "Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK" Mol. Cell. Biol. 14: 147-155

    PubMed  CAS  Google Scholar 

  29. Xing, Z., Chen, H.C., Nowlen, J.K., Taylor, S., Shalloway, D, Guan, JL (1994) "Direct interaction of v-Src with the focal adhesion kinase mediated by the Src SH2 domain" Mol. Biol. Cell 5: 413-421

    PubMed  CAS  Google Scholar 

  30. Chen, H.C., Guan, J.L. (1994) "Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase" Proc. Natl. Acad. Sci. USA 91: 10148-10152

    Article  PubMed  CAS  Google Scholar 

  31. Chen, H.C., Appeddu, P.A., Isoda, H., Guan, J.L. (1996) "Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase" J. Biol. Chem. 271: 26329-26334

    Article  PubMed  CAS  Google Scholar 

  32. Zhang, X., Chattopadhyay, A., Ji, Q.S., Owen, J.D., Ruest, P.J., Carpenter, G., Hanks, S.K. (1999) "Focal adhesion kinase promotes phospholipase C-gamma1 activity" Proc. Natl. Acad. Sci. USA 96: 9021-9026

    Article  PubMed  CAS  Google Scholar 

  33. Han, D.C., Guan, J.L. (1999) "Association of focal adhesion kianse with Grb7 and its role in cell migration" J. Biol. Chem. 274: 24425-24430

    Article  PubMed  CAS  Google Scholar 

  34. Calalb, M.B., Polte, T.R., Hanks, S.K. (1995) "Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases" Mol. Cell. Biol. 15: 954-963

    PubMed  CAS  Google Scholar 

  35. Schlaepfer, D.D., Hanks, S.K., Hunter, T., der Geer, P. (1994) "Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase" Nature 372: 786-791

    PubMed  CAS  Google Scholar 

  36. Schlaepfer, D.D., Hunter, T. (1996) "Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases" Mol. Cell. Biol. 16: 5623-5633

    PubMed  CAS  Google Scholar 

  37. Schaller, M.D., Parsons, J.T. (1995) "pp125FAK-depenmdnet tyrosine phosphorylation of paxillin creates a high-affinity binding site for Crk" Mol. Cell. Biol. 15: 2635-2645

    PubMed  CAS  Google Scholar 

  38. Ruest, P.J., Shin, N.Y., Polte, T.R., Zhang, X. (2001) "Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src" Mol. Cell. Biol. 21: 7641-7652

    Article  PubMed  CAS  Google Scholar 

  39. Reynolds, A.B., Kanner, S.B., Wang, H.C., Parsons, J.T. (1989) "Stable association of activated pp60src with two tyrosine-phosphorylated cellular proteins" Mol. Cell. Biol. 9: 3951-3958

    PubMed  CAS  Google Scholar 

  40. Matsuda, M., Mayer, B.J., Fukui, Y., Hanafusa, H. (1990) "Binding of transforming protein, p47gag-crk, to a broad range of phosphotyrosine-containing proteins" Science 248: 1537-1539

    Article  PubMed  CAS  Google Scholar 

  41. Sakai, R., Iwamatsu, A., Hirano, N., Ogawa, S., Tanaka, T., Mano, H., Yazaki, Y., Hirai, H. (1994) "A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner" EMBO J. 13: 3748-3756

    PubMed  CAS  Google Scholar 

  42. Nakamoto, T., Sakai, R., Ozawa, K., Yazaki, Y., Hirai, H. (1996) "Direct binding of C-terminal region of p130Cas to SH2 and SH3 domains of Src kinase" J. Biol. Chem. 271: 8959-8965

    Article  PubMed  CAS  Google Scholar 

  43. Polte, T.R., Hanks, S.K. (1995) "Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas" Proc. Natl. Acad. Sci. USA 92: 10678-10682

    Article  PubMed  CAS  Google Scholar 

  44. Kirsch, K.H., Georgescu, M.M., Hanafusa, H. (1998) "Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G" J. Biol. Chem. 273: 25673-25679

    Article  PubMed  CAS  Google Scholar 

  45. Garton, A.J., Burnham, M.R., Bouton, A.H., Tonks, N.K. (1997) "Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition" Oncogene 15: 877-885

    Article  PubMed  CAS  Google Scholar 

  46. Honda, H., Oda, H., Nakamoto, T., Honda, Z., Kakai, R., Suzuki, T., Saito, T., Nakamura, K., Nakao, K., Ishikawa, T., Katsuki, M., Yazaki, Y., Hirai, H. (1998) "Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas" Nat. Genet. 19: 361-365

    Article  PubMed  CAS  Google Scholar 

  47. Cary, L.A., Han, D.C., Polte, T., Hanks, S.K., Guan, J.L. (1998) "Identification of p130Cas as a mediator of focal adhesion kinase-promoted cell migration" J. Cell Biol. 140: 211-221

    Article  PubMed  CAS  Google Scholar 

  48. Lai, J.F., Kao, S.C., Jiang, S.T., Tang, M.J., Chan, P.C., Chen, H.C. (2000) "Involvement of focal adhesion kianse in hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells" J. Biol. Chem. 275: 7474-7480

    Article  PubMed  CAS  Google Scholar 

  49. Owen, J.D., Ruest, P.J., Fry, D.W., Hanks, S.K. (1999) "Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto-and activation loop phosphorylation sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2" Mol. Cell. Biol. 19: 4806-4818

    PubMed  CAS  Google Scholar 

  50. Cheng, C.H., Hsieh, C.L., Shu, K.H., Chen, Y.L., Chen, H.C. (2002) "Effect of calcium channel antagonist diltiazem and calcium ionophore A23187 on cyclosporine A-induced apoptosis of renal tubular cells" FEBS Lett. 516: 191-196

    Article  PubMed  CAS  Google Scholar 

  51. Chan, P.C., Liang, C.C., Yu, K.C., Chang, M.C., Ho, W.L., Chen, B.H., Chen, H.C. (2002) "Synergistic effect of focal adhesion kinase overexpression and hepatocyte growth factor stimulation on cell transformation" J. Biol. Chem. 277: 50373-50379

    Article  PubMed  CAS  Google Scholar 

  52. Reginato, M.J., Mills, K.R., Paulus, J.K., Lynch, D.K., Sgroi, D.C., Debnath, J., Muthuswamy, S.K., Brugge, J.S. (2003) "Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis" Nat. Cell Biol. 5: 733-740

    Article  PubMed  CAS  Google Scholar 

  53. Windham, T.C., Parikh, N.U., Sieak, D.R., Summy, J.M., McConkey, D.J., Kraker, A.J., Gallick, G.E. (2002) "Src activation regulates anoikis in human colon tumor cell lines" Oncogene 21: 7797-7807

    Article  PubMed  CAS  Google Scholar 

  54. Roy, S., Ruest, P.J., Hanks, S.K. (2002) "FAK regulates tyrosine phosphorylation of CAS, paxillin, and PYK2 in cells expressing v-Src, but is not a critical determinant of v-Src transformation" J. Cell. Biochem. 84: 377-388

    Article  PubMed  CAS  Google Scholar 

  55. Carragher, N.O., Westhoff, M.A., Riley, D., Potter, D.A., Dutt, P., Elce, J.S., Greer, P.A., Frame, M.C. (2002) "v-Src- induced modulation of the calpain-calpastatin proteolytic system regulates transformation" Mol. Cell. Biol. 22: 257-269

    Article  PubMed  CAS  Google Scholar 

  56. Hauck, C.R., Hsia, D.A., Puente, X.S., Cheresh, D.A., Schlaepfer, D.D. (2002) "FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth" EMBO J. 21: 6289-6302

    Article  PubMed  CAS  Google Scholar 

  57. Hsia, D.A., Mitra, S.K., Hauck, C.R., Streblow, D.N., Nelson, J.A., Ilic, D., Huang, S., Li, E., Nemerow, G.R., Leng, J., Spencer, K.S.R., Cheresh, D.A., Schlaepfer, D.D. (2003) "Differential regulation of cell motility and invasion by FAK" J. Cell Biol. 160: 753-767

    Article  PubMed  CAS  Google Scholar 

  58. McLean, G.W., Fincham, V.J., Frame, M.C. (2000) "v-Src induces tyrosine phosphorylation of focal adhesion kinase independently of tyrosine 397 and formation a complex with Src" J. Biol. Chem. 275: 23333-23339

    Article  PubMed  CAS  Google Scholar 

  59. Keely, P.J., Westwick, J.K., Whitehead, I.P., Der, C.J., Parise, L.V. (1997) "Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K" Nature 390: 632-636

    Article  PubMed  CAS  Google Scholar 

  60. Shaw, L.M., Rabinovitz, I., Wang, H.H.F., Toker, A., Mercurio, A.M. (1997) "Activation of phosphoinositide 3-OH kinase by the α6β4 integrin promotes carcinoma invasion" Cell 91: 949-960

    Article  PubMed  CAS  Google Scholar 

  61. Kim, D., Kim, S., Koh, H., Yoon, S.O., Chung, A.S., Cho, K.S., Chung, J. (2001) "Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production" FASEB J. 15: 1953-1962

    Article  PubMed  CAS  Google Scholar 

  62. Goldberg, G.S., Alexander, D.B., Pellicena, P., Zhang, Z.Y., Tsuda, H., Miller, W.T. (2003) "Src phosphorylates Cas on Tyrosine 253 to promote migration of transformed cells" J. Biol. Chem. 278: 46533-46540

    Article  PubMed  CAS  Google Scholar 

  63. Cheng, C.H., Yu, K.C., Chen, H.L., Chen, S.Y., Huang, C.H., Chan, P.C., Wung, C.W., Chen, H.C. (2004) "Blockade of v-Src-stimulated tumor formation by the Src homolog 3 domain of Crk-associated substrate" FEBS Lett. 557: 221-227

    Article  PubMed  CAS  Google Scholar 

  64. Li, E., Stupack, D.G., Brown, S.L., Klemke, R., Schlaepfer, D.D., Nemerow, G.R. (2000) "Association of p130Cas with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry" J. Biol. Chem. 275: 14729-14735

    Article  PubMed  CAS  Google Scholar 

  65. Hakak, Y., Martin, S. (1999) "Cas mediates transcriptional activation of the serum response element by Src" J. Cell. Biol. 19: 6953-6962

    CAS  Google Scholar 

  66. Dolfi, F., Garcia-Guaman, M., Ojaniemi, M., Nakamura, H., Matsuda, M., Vuori, K. (1998) "The adaptor protein Crk connects multiple cellular stimuli to the JNK signaling pathway" Proc. Natl. Acad. Sci. USA 95: 15394-15399

    Article  PubMed  CAS  Google Scholar 

  67. Schwartz, M.A. (1997) "Integrins, oncogenes, and anchorage independence" J. Cell Biol. 139: 575-578

    Article  PubMed  CAS  Google Scholar 

  68. Wei, L., Yang, Y., Zhang, X., Yu, Q. (2004) "Cleavage of p130Cas in anoikis" J. Cell. Biochem. 91: 325-335

    Article  PubMed  CAS  Google Scholar 

  69. Moissoglu, K., Gelman, I.H. (2003) "v-Src rescues actin-based cytoskeletal architecture and cell motility and incuces enhanced anchorage independence during oncogenic transformation of focal adhesion kinase-null fibroblasts" J. Biol. Chem. 278: 47946-47959

    Article  PubMed  CAS  Google Scholar 

  70. Westhoff, M.A., Serrels, B., Fincham, V.J., Frame, M.C., Carragher, N.O. (2004) "Src-mediated phosphorylation of focal adhesion kinase couples actin and adhesion dynamics to survival signaling" Mol. Cell. Biol. 24: 8113-8133

    Article  PubMed  CAS  Google Scholar 

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Chang, LC., Huang, CH., Cheng, CH. et al. Differential Effect of the Focal Adhesion Kinase Y397F Mutant on v-Src-Stimulated Cell Invasion and Tumor Growth. J Biomed Sci 12, 571–585 (2005). https://doi.org/10.1007/s11373-005-7212-5

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