DISCOVERIES (ISSN 2359-7232), 2016, April-June issue


Plow EF, Das M, Bialkowska K, Sossey-Alaoui K. Of Kindlins and Cancer. Discoveries 2016, April-June; 4(2): e59. DOI: 10.15190/d.2016.6

Submitted: June 10, 2016; Revised: June 29, 2016; Accepted: June 29, 2016; Published: June 30, 2016;

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Of Kindlins and Cancer

Edward F. Plow*, Mitali Das, Katarzyna Bialkowska, Khalid Sossey-Alaoui*

Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

*Correspondence to: Edward F. Plow, PhD and Khalid Sossey-Alaoui, PhD, Department of Molecular Cardiology/NB5-50, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, Phone: 1-216-445-8200; Emails: and 


Kindlins are 4.1-ezrin-ridixin-moesin (FERM) domain containing proteins. There are three kindlins in mammals, which share high sequence identity.  Kindlin-1 is expressed primarily in epithelial cells, kindlin-2 is widely distributed and is particularly abundant  in adherent cells, and kindlin-3 is expressed primarily in hematopoietic cells. These distributions are not exclusive; some cells express multiple kindlins, and transformed cells often exhibit aberrant expression, both in the isoforms and the levels of kindlins. Great interest in the kindlins has emerged from the recognition from that they play major roles in controlling integrin function.  In vitro studies, in vivo studies of mice deficient in kindlins, and studies of patients with genetic deficiencies of kindlins have clearly established that they regulate the capacity of integrins to mediate their functions. Kindlins are adaptor proteins; their function emanate from their interaction with binding partners, including the cytoplasmic tails of integrins and components of the actin cytoskeleton. The purpose of this review is to provide a brief overview of kindlin structure and function, a consideration of their binding partners, and then to focus on the relationship of each kindlin family member with cancer. In view of many correlations of kindlin expression levels and neoplasia and the known association of integrins with tumor progression and metastasis, we consider whether regulation of kindlins or their function would be attractive targets for treatment of cancer. 

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1. Larjava H, Plow EF, Wu C. Kindlins: essential regulators of integrin signalling and cell-matrix adhesion. EMBO Rep. 2008 Nov 7;9:1203-8.

2. Plow EF, Qin J, Byzova T. Kindling the flame of integrin activation and function with kindlins. Curr.Opin.Hematol. 2009 Sep;16(5):323-8. 

3. Meves A, Stremmle C, Gottschalk K, Fassler R. The Kindlin protein family: new members to the club of focal adhesion proteins. Trends Cell Biol. 2009 Aug 19;19(10).

4. Malinin NL, Plow E.F., Byzova TV. Kindlins in FERM adhesion. Blood 2010;115:4011-7.

5. Ye F, Petrich BG. Kindlin: helper, co-activator, or booster of talin in integrin activation? Curr. Opin. Hematol. 2011 Sep;18(5):356-60.

6. Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat.Rev.Mol.Cell Biol. 2010 Apr;11(4):288-300.

7. Ye F, Lagarrigue F, Ginsberg MH. SnapShot: talin and the modular nature of the integrin adhesome. Cell 2014 Mar 13;156(6):1340.

8. Khan AA, Janke A, Shimokawa T, Zhang H. Phylogenetic analysis of kindlins suggests subfunctionalization of an ancestral unduplicated kindlin into three paralogs in vertebrates. Evol.Bioinform.Online. 2011;7:7-19. 

9. Meller J, Rogozin IB, Poliakov E, Meller N, Bedanov-Pack M, Plow EF, et al.. Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness. Mol.Biol.Cell 2015 Feb 15;26(4):786-96. 

10. Siegel DH, Ashton GH, Penagos HG, Lee JV, Feiler HS, Wilhelmsen KC, et al. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. Am..J..Hum..Genet. 2003 Jul;.73(1):174-87

11. White SJ, McLean WH. Kindler surprise: mutations in a novel actin-associated protein cause Kindler syndrome. J.Dermatol.Sci. 2005 Jun;38(3):169-75.

12. Duperret EK, Ridky TW. Kindler syndrome in mice and men. Cancer Biol.Ther. 2014 Sep;15(9):1113-6. 

13. Ussar S, Moser M, Widmaier M, Rognoni E, Harrer C, Genzel-Boroviczeny O, et al. Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction. PLoS. Genet. 2008 Dec;4(12):e1000289.

14. Mory A, Feigelson SW, Yarali N, Kilic SS, Bayhan GI, Gershoni-Baruch R, et al. Kindlin-3: a new gene involved in the pathogenesis of LAD-III. Blood 2008 Sep 15;112(6):2591.

15. Kuijpers TW, van d, V, Weterman MA, de BM, Tool AT, van den Berg TK, et al. LAD-1/variant syndrome is caused by mutations in FERMT3. Blood 2009 Dec 8;113:4740-6.

16. Malinin NL, Zhang L, Choi J, Ciocea A, Razorenova O, Ma Y-Q, et al. A point mutation in kindlin-3 ablates activation of three integrin subfamilies in humans. Nature Med. 2009;15:313-8.

17. Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S, et al. Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nat. Med. 2009 Mar;15(3):306-12. 

18. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat. Med. 2008 Mar;14(3):325-30.

19. Dowling JJ, Gibbs E, Russell M, Goldman D, Minarcik J, Golden JA, et al. Kindlin-2 Is an essential component of intercalated discs and is required for vertebrate cardiac structure and function. Circ.Res. 2008;102:423-31.

20. Pluskota E, Dowling JJ, Gordon N, Golden JA, Szpak D, West XZ, et al. The integrin coactivator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish. Blood 2011 May 5;117(18):4978-87. 

21. Pluskota E, Ma Y, Bledzka K, Bialkowska K, Soloviev DA, Szpak D, et al. Kindlin-2 Regulates Hemostasis by Controlling Endothelial Cell Surface Expression of ADP/AMP Catabolic Enzymes via a Clathrin-Dependent Mechanism. Blood 2013 Oct 3;122:2491-9.

22. Bledzka K, Bialkowska K, Sossey-Alaoui K, Vaynberg J, Pluskota E, Qin J, et al. Kindlin-2 directly binds actin and regulates integrin outside-in signaling. J.Cell Biol. 2016 Apr 11;213(1):97-108. 

23. Ussar S, Wang HV, Linder S, Fassler R, Moser M. The Kindlins: subcellular localization and expression during murine development. Exp.Cell Res. 2006 Oct 1;312(16):3142-51.

24. Bialkowska K, Ma Y.Q., Bledzka K., Sossey-Alaoui K, Izem L, Zhang X, et al. The integrin coactivator kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell. J Biol. Chem. 2010;285:18640-9.

25. Goult BT, Bouaouina M, Harburger DS, Bate N, Patel B, Anthis NJ, et al. The structure of the N-terminus of kindlin-1: a domain important for alphaiibbeta3 integrin activation. J. Mol. Biol. 2009 Dec 18;394(5):944-56.

26. Perera D, Ma Y.Q., Yang J, Hirbawi J, Plow E.F., Qin J. Membrane Binding of the N-Terminal Ubiquitin-Like Domain of Kindlin-2 Is Crucial for Its Regulation of Integrin Activation. Structure 2011;19:1664-71.

27. Bouaouina M, Goult BT, Huet-Calderwood C, Bate N, Brahme NN, Barsukov IL, et al. A conserved lipid-binding loop in the kindlin FERM F1 domain is required for kindlin-mediated alphaIIbbeta3 integrin coactivation. J. Biol. Chem. 2012 Mar 2;287(10):6979-90. 

28. Yan M, Zhang L, Wu Y, Gao L, Yang W, Li J, et al. Increased expression of kindlin-2 is correlated with hematogenous metastasis and poor prognosis in patients with clear cell renal cell carcinoma. FEBS Open Bio. 2016; 1-15. 

29. Qu H, Tu Y, Shi X, Larjava H, Saleem MA, Shattil SJ, et al. Kindlin-2 regulates podocyte adhesion and fibronectin matrix deposition through interactions with phosphoinositides and integrins. J. Cell Sci. 2011 Mar 15;124(Pt 6):879-91. 

30. Liu J, Fukuda K, Xu Z, Ma Y.Q., Hirbawi J, Mao X, et al. Structural Basis of Phosphoinositide Binding to Kindlin-2 Pleckstrin Homology Domain in Regulating Integrin Activation. J Biol. Chem. 2011;286:43334-42.

31. Fukuda K, Bledzka K, Yang J, Perera HD, Plow EF, Qin J. Molecular basis of kindlin-2 binding to integrin-linked kinase pseudokinase for regulating cell adhesion. J Biol. Chem. 2014 Oct 10;289(41):28363-75. 

32. Huet-Calderwood C, Brahme NN, Kumar N, Stiegler AL, Raghavan S, Boggon TJ, et al. Differences in binding to the ILK complex determines kindlin isoform adhesion localization and integrin activation. J Cell Sci. 2014 Oct 1;127(Pt 19):4308-21. 

33. Theodosiou M, Widmaier M, Bottcher RT, Rognoni E, Veelders M, Bharadwaj M, et al. Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin. Elife. 2016;5:e10130. 

34. Xu Z, Chen X, Zhi H, Gao J, Bialkowska K, Byzova TV, et al. Direct Interaction of Kindlin-3 With Integrin alphaIIbbeta3 in Platelets Is Required for Supporting Arterial Thrombosis in Mice. Arterioscler. Thromb. Vasc. Biol. 2014 Jun 26;9:1961-7.

35. Xu Z, Gao J, Hong J, Ma YQ. Integrity of kindlin-2 FERM subdomains is required for supporting integrin activation. Biochem.Biophys.Res.Commun. 2013 May 3;434(2):382-7.

36. Kasirer-Friede A, Kang J, Kahner B, Ye F, Ginsberg MH, Shattil SJ. ADAP interactions with talin and kindlin promote platelet integrin alphaIIbbeta3 activation and stable fibrinogen binding. Blood 2014 Feb 12;20:3156-65.

37. Feng C, Li YF, Yau YH, Lee HS, Tang XY, Xue ZH, et al. Kindlin-3 mediates integrin alphaLbeta2 outside-in signaling, and it interacts with scaffold protein receptor for activated-C kinase 1 (RACK1). J. Biol. Chem. 2012 Mar 30;287(14):10714-26. 

38. Liu Z, Lu D, Wang X, Wan J, Liu C, Zhang H. Kindlin-2 phosphorylation by Src at Y193 enhances Src activity and is involved in Migfilin recruitment to the focal adhesions. FEBS Lett. 2015 Jul 8;589(15):2001-10.

39. Yu Y, Wu J, Wang Y, Zhao T, Ma B, Liu Y, et al. Kindlin 2 forms a transcriptional complex with beta-catenin and TCF4 to enhance Wnt signalling. EMBO Rep. 2012 Aug;13(8):750-8.

40. Bialkowska K, Byzova TV, Plow EF. Site-specific phosphorylation of kindlin-3 protein regulates its capacity to control cellular responses mediated by integrin alphaIIbbeta3. J. Biol. Chem. 2015 Mar 6;290(10):6226-42.

41. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000;407:258-64

42. Remijn JA, Wu YP, Jeninga EH, IJsseldijk MJ, van WG, de Groot PG, et al. Role of ADP receptor P2Y(12) in platelet adhesion and thrombus formation in flowing blood. Arterioscler. Thromb. Vasc. Biol. 2002 Apr 1;22(4):686-91.

43. Byzova TV, Goldman CK, Pampori N, Thomas KA, Bett A, Shattil SJ, et al. A mechanism for modulation of cellular responses to VEGF: activation of the integrins. Mol. Cell 2000;6:851-60

44. Katsumi A, Orr AW, Tzima E, Schwartz MA. Integrins in mechanotransduction. J. Biol. Chem. 2004 Mar 26;279(13):12001-4.

45. Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood 1994;84:2068-101.

46. Diamond MS, Springer TA. The dynamic regulation of integrin adhesiveness. Curr. Biol. 1994;4:506-17.

47. Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA. Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the b2 integrin CD11b/CD18. Blood 1996;88:146-57.

48. Ehlers R, Ustinov V, Chen Z, Zhang X, Rao R, Luscinskas FW, Lopez J, et al. Targeting platelet-leukocyte interactions: identification of the integrin Mac-1 binding site for the platelet counter receptor glycoprotein Iba. J. Exp. Med. 2003;198:1077-88.

49. Marguerie GA, Plow EF. The fibrinogen dependent pathway of platelet aggregation. Ann.N.Y.Acad.Sci. 1983;408:556-67.

50. Bledzka K, Liu J, Xu Z, Perera HD, Yadav SP, Bialkowska K, et al. Spatial coordination of kindlin-2 with talin head domain in interaction with integrin beta cytoplasmic tails. J. Biol. Chem. 2012 Jul 13;287(29):24585-94. 

51. Schurpf T, Springer TA. Regulation of integrin affinity on cell surfaces. EMBO J. 2011 Nov 30;30(23):4712-27. 

52. Karakose E, Schiller HB, Fassler R. The kindlins at a glance. J.Cell Sci. 2010 Jul 15;123(Pt 14):2353-6.

53. Plow EF, Meller J, Byzova TV. Integrin function in vascular biology: a view from 2013. Curr .Opin. Hematol. 2014 May; 21(3):241-7.

54. Pluskota E, Ma Y, Bledzka KM, Bialkowska K, Soloviev DA, Szpak D, et al. Kindlin-2 regulates hemostasis by controlling endothelial cell-surface expression of ADP/AMP catabolic enzymes via a clathrin-dependent mechanism. Blood 2013 Oct 3;122(14):2491-9. 

55. Rognoni E, Widmaier M, Jakobson M, Ruppert R, Ussar S, Katsougkri D, et al. Kindlin-1 controls Wnt and TGF-beta availability to regulate cutaneous stem cell proliferation. Nat. Med. 2014 Apr;20(4):350-9. 

56. Sossey-Alaoui K, Pluskota E, Davuluri G, Bialkowska K, Das M, Szpak D, et al. Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis. FASEB J. 2014 May;28(5):2260-71. 

57. Weinstein EJ, Bourner M, Head R, Zakeri H, Bauer C, Mazzarella R. URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas. Biochim.Biophys.Acta 2003 Apr 17;1637(3):207-16.

58. Bauer R, Ratzinger S, Wales L, Bosserhoff A, Senner V, Grifka J, et al. Inhibition of collagen XVI expression reduces glioma cell invasiveness. Cell Physiol Biochem. 2011;27(3-4):217-26.

59. Mahawithitwong P, Ohuchida K, Ikenaga N, Fujita H, Zhao M, Kozono S, et al. Kindlin-1 expression is involved in migration and invasion of pancreatic cancer. Int.J.Oncol. 2013 Apr;42(4):1360-6.

60. Sin S, Bonin F, Petit V, Meseure D, Lallemand F, Bieche I, et al. Role of the focal adhesion protein kindlin-1 in breast cancer growth and lung metastasis. J. Natl. Cancer Inst. 2011 Sep 7;103(17):1323-37.

61. Ma HX, Shu QH, Pan JJ, Liu D, Xu GL, Li JS, et al. Expression of Kindlin-1 in human hepatocellular carcinoma and its prognostic significance. Tumour Biol. 2015 Jun;36(6):4235-41.

62. Bedal KB, Grassel S, Oefner PJ, Reinders J, Reichert TE, Bauer R. Collagen XVI induces expression of MMP9 via modulation of AP-1 transcription factors and facilitates invasion of oral squamous cell carcinoma. PLoS.One. 2014;9(1): e86777. 

63. Mizutani H, Masuda K, Nakamura N, Takenaka H, Tsuruta D, Katoh N. Cutaneous and laryngeal squamous cell carcinoma in mixed epidermolysis bullosa, kindler syndrome. Case. Rep. Dermatol. 2012 May;4(2):133-8. 

64. Zhan J, Zhu X, Guo Y, Wang Y, Wang Y, Qiang G, et al. Opposite role of Kindlin-1 and Kindlin-2 in lung cancers. PLoS One. 2012;7(11):e50313. 

65. An Z, Dobra K, Lock JG, Stromblad S, Hjerpe A, Zhang H. Kindlin-2 is expressed in malignant mesothelioma and is required for tumor cell adhesion and migration. Int. J. Cancer 2010 Nov 1;127(9):1999-2008.

66. Ashton GH. Kindler syndrome. Clin. Exp. Dermatol. 2004 Mar;29(2):116-21.

67. Arita K, Wessagowit V, Inamadar AC, Palit A, Fassihi H, Lai-Cheong JE, et al. Unusual molecular findings in Kindler syndrome. Br. J. Dermatol. 2007 Dec;157(6):1252-6.

68. Lai-Cheong JE, Tanaka A, Hawche G, Emanuel P, Maari C, Taskesen M, et al. Kindler syndrome: a focal adhesion genodermatosis. Br. J. Dermatol. 2009 Feb;160(2):233-42.

69. Emanuel PO, Rudikoff D, Phelps RG. Aggressive squamous cell carcinoma in Kindler syndrome. Skinmed. 2006 Nov;5(6):305-7.

70. Has C, Herz C, Zimina E, Qu HY, He Y, Zhang ZG, et al. Kindlin-1 Is required for RhoGTPase-mediated lamellipodia formation in keratinocytes. Am. J. Pathol. 2009 Oct;175(4):1442-52. 

71. Lotem M, Raben M, Zeltser R, Landau M, Sela M, Wygoda M, et al. Kindler syndrome complicated by squamous cell carcinoma of the hard palate: successful treatment with high-dose radiation therapy and granulocyte-macrophage colony-stimulating factor. Br. J. Dermatol. 2001 Jun;144(6):1284-6.

72. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011 Mar 4;144(5):646-74.

73. Kloeker S, Major MB, Calderwood DA, Ginsberg MH, Jones DA, Beckerle MC. The Kindler syndrome protein is regulated by transforming growth factor-beta and involved in integrin-mediated adhesion. J. Biol. Chem. 2004 Feb 20;279(8):6824-33.

74. Yang JR, Pan TJ, Yang H, Wang T, Liu W, Liu B, et al. Kindlin-2 promotes invasiveness of prostate cancer cells via NF-kappaB-dependent upregulation of matrix metalloproteinases. Gene 2016 Jan 15;576(1 Pt 3):571-6.

75. Sossey-Alaoui K, Plow EF. miR-138-Mediated Regulation of KINDLIN-2 Expression Modulates Sensitivity to Chemotherapeutics. Mol. Cancer Res. 2016 Feb;14(2):228-38. 

76. Gao J, Khan AA, Shimokawa T, Zhan J, Stromblad S, Fang W, et al. A feedback regulation between Kindlin-2 and GLI1 in prostate cancer cells. FEBS Lett. 2013 Mar 18;587(6):631-8.

77. Gong X, An Z, Wang Y, Guan L, Fang W, Stromblad S, et al. Kindlin-2 controls sensitivity of prostate cancer cells to cisplatin-induced cell death. Cancer Lett. 2010 Dec 18;299(1):54-62.

78. Yu Y, Wu J, Guan L, Qi L, Tang Y, Ma B, et al. Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family. Int. J. Cancer 2013 Sep 15;133(6):1368-79.

79. Zhao T, Guan L, Yu Y, Pei X, Zhan J, Han L, et al. Kindlin-2 promotes genome instability in breast cancer cells. Cancer Lett. 2013 Apr 28;330(2):208-16.

80. Guo B, Gao J, Zhan J, Zhang H. Kindlin-2 interacts with and stabilizes EGFR and is required for EGF-induced breast cancer cell migration. Cancer Lett. 2015 Jun 1;361(2):271-81.

81. Shen Z, Ye Y, Kauttu T, Seppanen H, Vainionpaa S, Wang S, et al. The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer cells mediated by tumor-associated macrophages. Oncol. Rep. 2013 Feb;29(2):791-7.

82. Ren Y, Jin H, Xue Z, Xu Q, Wang S, Zhao G, et al. Kindlin-2 inhibited the growth and migration of colorectal cancer cells. Tumour Biol. 2015 Jun;36(6):4107-14.

83. Mahawithitwong P, Ohuchida K, Ikenaga N, Fujita H, Zhao M, Kozono S, et al. Kindlin-2 expression in peritumoral stroma is associated with poor prognosis in pancreatic ductal adenocarcinoma. Pancreas 2013 May;42(4):663-9.

84. Zhan J, Song J, Wang P, Chi X, Wang Y, Guo Y, et al. Kindlin-2 induced by TGF-beta signaling promotes pancreatic ductal adenocarcinoma progression through downregulation of transcriptional factor HOXB9. Cancer Lett. 2015 May 28;361(1):75-85.

85. Ren C, Du J, Xi C, Yu Y, Hu A, Zhan J, et al. Kindlin-2 inhibits serous epithelial ovarian cancer peritoneal dissemination and predicts patient outcomes. Biochem.Biophys.Res.Commun. 2014 Mar 28;446(1):187-94.

86. Yang M, Du J, Lu D, Ren C, Shen H, Qiao J, et al. Increased expression of kindlin 2 in luteinized granulosa cells correlates with androgen receptor level in patients with polycystic ovary syndrome having hyperandrogenemia. Reprod. Sci. 2014 Jun;21(6):696-703. 

87. Zhang HF, Alshareef A, Wu C, Li S, Jiao JW, Cao HH, et al. Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin beta1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism. Oncotarget. 2015 Oct 6;6(30):28949-60. 

88. Cao HH, Zhang SY, Shen JH, Wu ZY, Wu JY, Wang SH, et al. A three-protein signature and clinical outcome in esophageal squamous cell carcinoma. Oncotarget. 2015 Mar 10;6(7):5435-48. 

89. Zhang HF, Zhang K, Liao LD, Li LY, Du ZP, Wu BL, et al. miR-200b suppresses invasiveness and modulates the cytoskeletal and adhesive machinery in esophageal squamous cell carcinoma cells via targeting Kindlin-2. Carcinogenesis 2014 Feb;35(2):292-301.

90. Ge YS, Liu D, Jia WD, Li JS, Ma JL, Yu JH, et al. Kindlin-2: a novel prognostic biomarker for patients with hepatocellular carcinoma. Pathol. Res. Pract. 2015 Mar;211(3):198-202.

91. Ou YW, Zhao ZT, Wu CY, Xu BN, Song YM, Zhan QM. Mig-2 attenuates cisplatin-induced apoptosis of human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways. Acta Pharmacol. Sin. 2014 Sep;35(9):1199-206. 

92. Shen Z, Ye Y, Kauttu T, Seppanen H, Vainionpaa S, Wang S, et al. Novel focal adhesion protein kindlin-2 promotes the invasion of gastric cancer cells through phosphorylation of integrin beta1 and beta3. J. Surg.Oncol. 2013 Aug;108(2):106-12.

93. Shen Z, Ye Y, Dong L, Vainionpaa S, Mustonen H, Puolakkainen P, et al. Kindlin-2: a novel adhesion protein related to tumor invasion, lymph node metastasis, and patient outcome in gastric cancer. Am. J. Surg. 2012 Feb;203(2):222-9.

94. Talaat S, Somji S, Toni C, Garrett SH, Zhou XD, Sens MA, et al. Kindlin-2 expression in arsenite- and cadmium-transformed bladder cancer cell lines and in archival specimens of human bladder cancer. Urology 2011 Jun;77(6):1507. 

95. Wu WB, Zhang Q, Li Y, Shan SL, Li XY, Tian Z, Tet al. [Expression of Kindlins and angiopoietins in acute myeloid leukemia]. Zhongguo Shi Yan.Xue.Ye.Xue.Za Zhi. 2012 Feb;20(1):7-11

96. Qu J, Ero R, Feng C, Ong LT, Tan HF, Lee HS, et al. Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells. Sci.Rep. 2015;5:18491. 

97. Djaafri I, Khayati F, Menashi S, Tost J, Podgorniak MP, Sadoux A, et al. A novel tumor suppressor function of Kindlin-3 in solid cancer. Oncotarge. 2014 Oct 15;5(19):8970-85.

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  • 2016, January | Main Objective

    After reaching all proposed milestones until now (including being indexed by Google Scholar in 2014), Discoveries' next Aim is PubMed indexing of all its articles (already published and upcoming). There will be no charge for the submission or publication of articles before Discoveries is indexed.

  • 2015, August | Discoveries - on PubMed

    We are happy to announce that our first Discoveries articles were included in PMC and PubMed. More articles (submitted by NIH funded authors) are now processed for being included.

    Discoveries articles now on PubMed
  • 2015, April | Special Issue

    DISCOVERIES published the SPECIAL ISSUE entitled "INFLAMMATION BETWEEN DEFENSE AND DISEASE: Impact on Tissue Repair and Chronic Sickness".

    Special Issue on "Inflammation"
  • 2015 | Ischemia Collection

    DISCOVERIES launched a call for papers for a Collection of Articles with focus on "ISCHEMIA". If you are interested to submit a manuscript, please contact us at

  • 2014, September | Special Issue

    DISCOVERIES just publish the SPECIAL ISSUE entitled "CELL SECRETION & MEMBRANE FUSION" in September 2014. Initially scheduled for publication between October 2014-March 2015, this issue was successfully published earlier than scheduled. 

    Special Issue
  • 2014, April | Indexed by Google Scholar

    All our published articles are now indexed by Google Scholar! First citations to Discoveries articles are included! Search for the article's title (recommended) or the authors:

    Google Scholar Search
  • 2014 | DISCOVERIES

    DOIs (Digital Object Identifiers) are now assigned to all our published manuscripts in Discoveries. DOI uniquely identifies an article and is provided by CrossRef.

  • 2013, July | Manuscript Submission

    Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)! There are NO fees for the manuscript submission or publishing of the accepted manuscripts.
    read more

  • 2013, July | DISCOVERIES

    We are now ACCEPTING MANUSCRIPTS for publishing in DISCOVERIES. We aim publishing a small number of high impact experimental articles & reviews (around 40/year) to maintain a high impact factor. Domains of interest: all areas related to Medicine, Biology and Chemistry ...

    read more
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