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DDRs: receptors that mediate adhesion, migration and invasion in breast cancer cells

Departamento de Biologia Celular, Cinvestav-IPN, Av IPN # 2508, San Pedro Zacatenco, DF 07360, Mexico

Special Issues: Cell Surface Receptors

Discoidin domain receptors (DDRs) are receptor tyrosine kinases that are activated by native collagens and have an important role during cell adhesion, development, differentiation, proliferation, and migration. DDR deregulation is associated with progression of several different cancers. However, there is limited information about the role of DDRs in the progression of breast cancer. In this review we attempt to collect the most relevant information about DDR signaling and their role in various cancer-related processes such as adhesion, epithelial to mesenchymal transition, migration, invasion, and survival, with a focus on breast cancer.
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1. Gjorevski N, Nelson CM (2011) Integrated morphodynamic signalling of the mammary gland. Nat Rev Mol Cell Biol 12: 581-593.    

2. Forsyth IA, Neville MC (2009) Introduction: hormonal regulation of mammary development and milk protein gene expression at the whole animal and molecular levels. J Mammary Gland Biol Neoplasia 14: 317-319.    

3. Polyak K, Kalluri R (2010) The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol 2: a003244.

4. Vogel WF, Abdulhussein R, Ford CE (2006) Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal 18: 1108-1116.    

5. Ozbek S, Balasubramanian PG, Chiquet-Ehrismann R, et al. (2010) The evolution of extracellular matrix. Mol Biol Cell 21: 4300-4305.    

6. Egeblad M, Rasch MG, Weaver VM (2010) Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol 22: 697-706.    

7. McNally S, Martin F (2011) Molecular regulators of pubertal mammary gland development. Ann Med 43: 212-234.    

8. Hinck L, Silberstein GB (2005) Key stages in mammary gland development: the mammary end bud as a motile organ. Breast Cancer Res 7: 245-251.    

9. Watson CJ (2006) Post-lactational mammary gland regression: molecular basis and implications for breast cancer. Expert Rev Mol Med 8: 1-15.

10. Brisken C, Kaur S, Chavarria TE, et al. (1999) Prolactin controls mammary gland development via direct and indirect mechanisms. Dev Biol 210: 96-106.    

11. Oakes SR, Rogers RL, Naylor MJ, et al. (2008) Prolactin regulation of mammary gland development. J Mammary Gland Biol Neoplasia 13: 13-28.    

12. Sternlicht MD, Kouros-Mehr H, Lu P, et al. (2006) Hormonal and local control of mammary branching morphogenesis. Differentiation 74: 365-381.    

13. Fata JE, Werb Z, Bissell MJ (2004) Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes. Breast Cancer Res 6: 1-11.

14. Myllyharju J, Kivirikko KI (2004) Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet 20: 33-43.    

15. Yeh YC, Lin HH, Tang MJ (2012) A tale of two collagen receptors, integrin beta1 and discoidin domain receptor 1, in epithelial cell differentiation. Am J Physiol Cell Physiol 303: C1207-1217.    

16. Carafoli F, Hohenester E (2013) Collagen recognition and transmembrane signalling by discoidin domain receptors. Biochim Biophys Acta 1834: 2187-2194.    

17. Valiathan RR, Marco M, Leitinger B, et al. (2012) Discoidin domain receptor tyrosine kinases: new players in cancer progression. Cancer Metastasis Rev 31: 295-321.    

18. Ortega N, Werb Z (2002) New functional roles for non-collagenous domains of basement membrane collagens. J Cell Sci 115: 4201-4214.    

19. Acerbi I, Cassereau L, Dean I, et al. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr Biol (Camb). [in press]

20. Tao G, Levay AK, Peacock JD, et al. Collagen XIV is important for growth and structural integrity of the myocardium. J Mol Cell Cardiol 53: 626-638.

21. Mehner C, Radisky DC (2013) Triggering the landslide: The tumor-promotional effects of myofibroblasts. Exp Cell Res 319: 1657-1662.    

22. Gehler S, Ponik SM, Riching KM, et al. (2013) Bi-directional signaling: extracellular matrix and integrin regulation of breast tumor progression. Crit Rev Eukaryot Gene Expr 23: 139-157.    

23. Nistico P, Bissell MJ, Radisky DC (2012) Epithelial-mesenchymal transition: general principles and pathological relevance with special emphasis on the role of matrix metalloproteinases. Cold Spring Harb Perspect Biol 4.

24. Favreau AJ, Vary CP, Brooks PC, et al. (2014) Cryptic collagen IV promotes cell migration and adhesion in myeloid leukemia. Cancer Med 3: 265-272.    

25. Emsley J, Knight CG, Farndale RW, et al. (2000) Structural basis of collagen recognition by integrin alpha2beta1. Cell 101: 47-56.    

26. Espinosa Neira R, Salazar EP (2012) Native type IV collagen induces an epithelial to mesenchymal transition-like process in mammary epithelial cells MCF10A. Int J Biochem Cell Biol 44: 2194-2203.    

27. Leitinger B (2011) Transmembrane collagen receptors. Annu Rev Cell Dev Biol 27: 265-290.    

28. Noordeen NA, Carafoli F, Hohenester E, et al. (2006) A transmembrane leucine zipper is required for activation of the dimeric receptor tyrosine kinase DDR1. J Biol Chem 281: 22744-22751.    

29. Mihai C, Chotani M, Elton TS, et al. (2009) Mapping of DDR1 distribution and oligomerization on the cell surface by FRET microscopy. J Mol Biol 385: 432-445.    

30. Shrivastava A, Radziejewski C, Campbell E, et al. (1997) An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol Cell 1: 25-34.    

31. Vogel W, Gish GD, Alves F, et al. (1997) The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell 1: 13-23.    

32. Canning P, Tan L, Chu K, et al. (2014) Structural mechanisms determining inhibition of the collagen receptor DDR1 by selective and multi-targeted type II kinase inhibitors. J Mol Biol 426: 2457-2470.    

33. Barker KT, Martindale JE, Mitchell PJ, et al. (1995) Expression patterns of the novel receptor-like tyrosine kinase, DDR, in human breast tumours. Oncogene 10: 569-575.

34. Di Marco E, Cutuli N, Guerra L, et al. (1993) Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal human tissues. J Biol Chem 268: 24290-24295.

35. Karn T, Holtrich U, Brauninger A, et al. (1993) Structure, expression and chromosomal mapping of TKT from man and mouse: a new subclass of receptor tyrosine kinases with a factor VIII-like domain. Oncogene 8: 3433-3440.

36. Fu HL, Valiathan RR, Arkwright R, et al. (2013) Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling. J Biol Chem 288: 7430-7437.    

37. Jin P, Zhang J, Sumariwalla PF, et al. (2008) Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res Ther 10: R73.    

38. Leitinger B (2014) Discoidin domain receptor functions in physiological and pathological conditions. Int Rev Cell Mol Biol 310: 39-87.    

39. Curat CA, Eck M, Dervillez X, et al. (2001) Mapping of epitopes in discoidin domain receptor 1 critical for collagen binding. J Biol Chem 276: 45952-45958.    

40. Abdulhussein R, McFadden C, Fuentes-Prior P, et al. (2004) Exploring the collagen-binding site of the DDR1 tyrosine kinase receptor. J Biol Chem 279: 31462-31470.    

41. Leitinger B (2003) Molecular analysis of collagen binding by the human discoidin domain receptors, DDR1 and DDR2. Identification of collagen binding sites in DDR2. J Biol Chem 278: 16761-16769.

42. Ichikawa O, Osawa M, Nishida N, et al. (2007) Structural basis of the collagen-binding mode of discoidin domain receptor 2. EMBO J 26: 4168-4176.    

43. Xu H, Raynal N, Stathopoulos S, et al. (2011) Collagen binding specificity of the discoidin domain receptors: binding sites on collagens II and III and molecular determinants for collagen IV recognition by DDR1. Matrix Biol 30: 16-26.    

44. Carafoli F, Mayer MC, Shiraishi K, et al. (2012) Structure of the discoidin domain receptor 1 extracellular region bound to an inhibitory Fab fragment reveals features important for signaling. Structure 20: 688-697.    

45. Leitinger B, Kwan AP (2006) The discoidin domain receptor DDR2 is a receptor for type X collagen. Matrix Biol 25: 355-364.    

46. Konitsiotis AD, Raynal N, Bihan D, et al. (2008) Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. J Biol Chem 283: 6861-6868.    

47. Koo DH, McFadden C, Huang Y, et al. (2006) Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1. FEBS Lett 580: 15-22.    

48. Wang CZ, Su HW, Hsu YC, et al. (2006) A discoidin domain receptor 1/SHP-2 signaling complex inhibits alpha2beta1-integrin-mediated signal transducers and activators of transcription 1/3 activation and cell migration. Mol Biol Cell 17: 2839-2852.    

49. Lemeer S, Bluwstein A, Wu Z, et al. (2012) Phosphotyrosine mediated protein interactions of the discoidin domain receptor 1. J Proteomics 75: 3465-3477.    

50. Ruiz PA, Jarai G (2011) Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and a JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts. J Biol Chem 286: 12912-12923.    

51. L'Hote C G, Thomas PH, Ganesan TS (2002) Functional analysis of discoidin domain receptor 1: effect of adhesion on DDR1 phosphorylation. FASEB J 16: 234-236.

52. Huang Y, Arora P, McCulloch CA, et al. (2009) The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA. J Cell Sci 122: 1637-1646.    

53. Shintani Y, Fukumoto Y, Chaika N, et al. (2008) Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J Cell Biol 180: 1277-1289.    

54. Hidalgo-Carcedo C, Hooper S, Chaudhry SI, et al. (2011) Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nat Cell Biol 13: 49-58.    

55. Hansen C, Greengard P, Nairn AC, et al. (2006) Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1. Exp Cell Res 312: 4011-4018.    

56. Hilton HN, Stanford PM, Harris J, et al. (2008) KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signalling. Biochim Biophys Acta 1783: 383-393.    

57. Dejmek J, Leandersson K, Manjer J, et al. (2005) Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival. Clin Cancer Res 11: 520-528.

58. Kim HG, Hwang SY, Aaronson SA, et al. (2011) DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1 activation. J Biol Chem 286: 17672-17681.    

59. Lu KK, Trcka D, Bendeck MP (2011) Collagen stimulates discoidin domain receptor 1-mediated migration of smooth muscle cells through Src. Cardiovasc Pathol 20: 71-76.    

60. Ongusaha PP, Kim JI, Fang L, et al. (2003) p53 induction and activation of DDR1 kinase counteract p53-mediated apoptosis and influence p53 regulation through a positive feedback loop. EMBO J 22: 1289-1301.    

61. Das S, Ongusaha PP, Yang YS, et al. (2006) Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappaB pathway activation. Cancer Res 66: 8123-8130.    

62. Ikeda K, Wang LH, Torres R, et al. (2002) Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen. J Biol Chem 277: 19206-19212.    

63. Yang K, Kim JH, Kim HJ, et al. (2005) Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation. J Biol Chem 280: 39058-39066.    

64. Olaso E, Labrador JP, Wang L, et al. (2002) Discoidin domain receptor 2 regulates fibroblast proliferation and migration through the extracellular matrix in association with transcriptional activation of matrix metalloproteinase-2. J Biol Chem 277: 3606-3613.    

65. Marcel V, Catez F, Diaz JJ (2015) p53, a translational regulator: contribution to its tumour-suppressor activity. Oncogene. [in press]

66. Petitjean A, Achatz MI, Borresen-Dale AL, et al. (2007) TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 26: 2157-2165.    

67. Vogel WF (2002) Ligand-induced shedding of discoidin domain receptor 1. FEBS Lett 514: 175-180.    

68. Slack BE, Siniaia MS, Blusztajn JK (2006) Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: involvement of Src tyrosine kinase. J Cell Biochem 98: 672-684.    

69. Fu HL, Sohail A, Valiathan RR, et al. (2013) Shedding of discoidin domain receptor 1 by membrane-type matrix metalloproteinases. J Biol Chem 288: 12114-12129.    

70. Shitomi Y, Thogersen IB, Ito N, et al. (2015) ADAM10 controls collagen signaling and cell migration on collagen by shedding the ectodomain of discoidin domain receptor 1 (DDR1). Mol Biol Cell 26: 659-673.    

71. Huber MA, Kraut N, Beug H (2005) Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 17: 548-558.    

72. Knust E, Bossinger O (2002) Composition and formation of intercellular junctions in epithelial cells. Science 298: 1955-1959.    

73. Yeh YC, Wu CC, Wang YK, et al. (2011) DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin. Mol Biol Cell 22: 940-953.    

74. Wang CZ, Yeh YC, Tang MJ (2009) DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading. Am J Physiol Cell Physiol 297: C419-429.    

75. Yeh YC, Wang CZ, Tang MJ (2009) Discoidin domain receptor 1 activation suppresses alpha2beta1 integrin-dependent cell spreading through inhibition of Cdc42 activity. J Cell Physiol 218: 146-156.    

76. Xu H, Bihan D, Chang F, et al. (2012) Discoidin domain receptors promote alpha1beta1- and alpha2beta1-integrin mediated cell adhesion to collagen by enhancing integrin activation. PLoS One 7: e52209.    

77. Imamichi Y, Menke A (2007) Signaling pathways involved in collagen-induced disruption of the E-cadherin complex during epithelial-mesenchymal transition. Cells Tissues Organs 185: 180-190.    

78. Staudinger LA, Spano SJ, Lee W, et al. (2013) Interactions between the discoidin domain receptor 1 and beta1 integrin regulate attachment to collagen. Biol Open 2: 1148-1159.    

79. Rudra-Ganguly N, Lowe C, Mattie M, et al. (2014) Discoidin domain receptor 1 contributes to tumorigenesis through modulation of TGFBI expression. PLoS One 9: e111515.    

80. Park CY, Min KN, Son JY, et al. (2014) An novel inhibitor of TGF-beta type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition. Cancer Lett 351: 72-80.    

81. Ozdamar B, Bose R, Barrios-Rodiles M, et al. (2005) Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science 307: 1603-1609.    

82. Buijs JT, Stayrook KR, Guise TA (2011) TGF-beta in the Bone Microenvironment: Role in Breast Cancer Metastases. Cancer Microenviron 4: 261-281.    

83. de Jong JS, van Diest PJ, van der Valk P, et al. (1998) Expression of growth factors, growth-inhibiting factors, and their receptors in invasive breast cancer. II: Correlations with proliferation and angiogenesis. J Pathol 184: 53-57.

84. Walsh LA, Nawshad A, Medici D (2011) Discoidin domain receptor 2 is a critical regulator of epithelial-mesenchymal transition. Matrix Biol 30: 243-247.    

85. Xu J, Lu W, Zhang S, et al. (2014) Overexpression of DDR2 contributes to cell invasion and migration in head and neck squamous cell carcinoma. Cancer Biol Ther 15: 612-622.    

86. Maeyama M, Koga H, Selvendiran K, et al. (2008) Switching in discoid domain receptor expressions in SLUG-induced epithelial-mesenchymal transition. Cancer 113: 2823-2831.    

87. Siziopikou KP (2013) Ductal carcinoma in situ of the breast: current concepts and future directions. Arch Pathol Lab Med 137: 462-466.    

88. Turashvili G, Bouchal J, Ehrmann J, et al. (2007) Novel immunohistochemical markers for the differentiation of lobular and ductal invasive breast carcinomas. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 151: 59-64.    

89. Toy KA, Valiathan RR, Nunez F, et al. (2015) Tyrosine kinase discoidin domain receptors DDR1 and DDR2 are coordinately deregulated in triple-negative breast cancer. Breast Cancer Res Treat 150: 9-18.    

90. Vogel WF, Aszodi A, Alves F, et al. (2001) Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Mol Cell Biol 21: 2906-2917.    

91. Ren T, Zhang J, Liu X, et al. (2013) Increased expression of discoidin domain receptor 2 (DDR2): a novel independent prognostic marker of worse outcome in breast cancer patients. Med Oncol 30: 397.    

92. Morikawa A, Takeuchi T, Kito Y, et al. (2015) Expression of Beclin-1 in the Microenvironment of Invasive Ductal Carcinoma of the Breast: Correlation with Prognosis and the Cancer-Stromal Interaction. PLoS One 10: e0125762.    

93. Zhang K, Corsa CA, Ponik SM, et al. (2013) The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nat Cell Biol 15: 677-687.    

94. Lodillinsky C, Infante E, Guichard A, et al. (2015) p63/MT1-MMP axis is required for in situ to invasive transition in basal-like breast cancer. Oncogene. [in press]

95. Xiang S, Liu YM, Chen X, et al. (2015) ZEB1 Expression Is Correlated With Tumor Metastasis and Reduced Prognosis of Breast Carcinoma in Asian Patients. Cancer Invest 33: 225.    

96. Ling J, Kumar R (2012) Crosstalk between NFkB and glucocorticoid signaling: a potential target of breast cancer therapy. Cancer Lett 322: 119-126.    

97. Koh M, Woo Y, Valiathan RR, et al. (2015) Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition. Int J Cancer 136: E508-520.    

98. Wolf K, Wu YI, Liu Y, et al. (2007) Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9: 893-904.    

99. Neuhaus B, Buhren S, Bock B, et al. (2011) Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors. Cell Mol Life Sci 68: 3757-3770.    

100.Jonsson M, Andersson T (2001) Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells. J Cell Sci 114: 2043-2053.

101. Gavin BJ, McMahon AP (1992) Differential regulation of the Wnt gene family during pregnancy and lactation suggests a role in postnatal development of the mammary gland. Mol Cell Biol 12: 2418-2423.

102. Dejmek J, Dib K, Jonsson M, et al. (2003) Wnt-5a and G-protein signaling are required for collagen-induced DDR1 receptor activation and normal mammary cell adhesion. Int J Cancer 103: 344-351.    

103. Roarty K, Serra R (2007) Wnt5a is required for proper mammary gland development and TGF-beta-mediated inhibition of ductal growth. Development 134: 3929-3939.    

104. Ribatti D, Crivellato E (2012) “Sprouting angiogenesis”, a reappraisal. Dev Biol 372: 157-165.    

105. Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284: 770-776.    

106. Dong Y, Li A, Wang J, et al. (2010) Synthetic lethality through combined Notch-epidermal growth factor receptor pathway inhibition in basal-like breast cancer. Cancer Res 70: 5465-5474.    

107. Thairu N, Kiriakidis S, Dawson P, et al. (2011) Angiogenesis as a therapeutic target in arthritis in 2011: learning the lessons of the colorectal cancer experience. Angiogenesis 14: 223-234.    

108. Yang Y, Sun M, Wang L, et al. (2013) HIFs, angiogenesis, and cancer. J Cell Biochem 114: 967-974.    

109. Ren T, Zhang W, Liu X, et al. (2014) Discoidin domain receptor 2 (DDR2) promotes breast cancer cell metastasis and the mechanism implicates epithelial-mesenchymal transition programme under hypoxia. J Pathol 234: 526-537.    

110. Rubinstein E (2011) The complexity of tetraspanins. Biochem Soc Trans 39: 501-505.    

111. Berditchevski F (2001) Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci 114: 4143-4151.

112. Powner D, Kopp PM, Monkley SJ, et al. (2011) Tetraspanin CD9 in cell migration. Biochem Soc Trans 39: 563-567.    

113. Miyake M, Nakano K, Ieki Y, et al. (1995) Motility related protein 1 (MRP-1/CD9) expression: inverse correlation with metastases in breast cancer. Cancer Res 55: 4127-4131.

114. Castro-Sanchez L, Soto-Guzman A, Navarro-Tito N, et al. (2010) Native type IV collagen induces cell migration through a CD9 and DDR1-dependent pathway in MDA-MB-231 breast cancer cells. Eur J Cell Biol 89: 843-852.    

115. Hansen RK, Bissell MJ (2000) Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones. Endocr Relat Cancer 7: 95-113.    

Copyright Info: © 2015, Eduardo Perez Salazar, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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