title: Dcas supports cell polarization and cell-cell adhesion complexes in development.
abstract: Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and beta-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Tikhmyanova
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tulin
authors.forename: Fabrice
authors.initials: F
authors.lastname: Roegiers
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
mesh_terms: D000483:Alleles; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D017353:Gene Deletion; D016023:Integrins / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000166:cytology; D009154:Mutation; D010641:Phenotype; D021381:Protein Transport; D013379:Substrate Specificity
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016023:Integrins; C110593:cas protein, Drosophila
references.citation: EMBO J. 2000 Dec 15;19(24):6759-69
references.pmid: 11118211
references.citation: Oncogene. 1995 Dec 7;11(11):2331-8
references.pmid: 8570184
references.citation: Cell Biochem Biophys. 2007;48(1):54-72
references.pmid: 17703068
references.citation: J Immunol. 2005 Sep 15;175(6):3492-501
references.pmid: 16148091
references.citation: Eur J Immunol. 2001 May;31(5):1417-27
references.pmid: 11465098
references.citation: Neuroscience. 2009 Sep 15;162(4):1106-19
references.pmid: 19464348
references.citation: J Biol Chem. 2002 Oct 18;277(42):39599-608
references.pmid: 12189134
references.citation: Development. 2004 Dec;131(23):5795-805
references.pmid: 15525665
references.citation: Nat Cell Biol. 2005 Oct;7(10):937-46
references.pmid: 16184168
references.citation: J Natl Cancer Inst. 2000 Jan 19;92(2):120-7
references.pmid: 10639513
references.citation: Dev Biol. 2002 Aug 1;248(1):29-39
references.pmid: 12142018
references.citation: Science. 2000 Jan 14;287(5451):324-7
references.pmid: 10634792
references.citation: Genes Dev. 1996 Mar 15;10(6):672-85
references.pmid: 8598295
references.citation: Oncogene. 2007 Feb 8;26(6):893-904
references.pmid: 16909115
references.citation: Oncogene. 2006 Mar 16;25(12):1721-32
references.pmid: 16288224
references.citation: J Immunol. 2003 Jan 15;170(2):969-78
references.pmid: 12517963
references.citation: Mol Cancer Res. 2005 Jun;3(6):307-15
references.pmid: 15972849
references.citation: Dev Biol. 1999 Apr 1;208(1):233-43
references.pmid: 10075855
references.citation: Cancer J. 2003 Mar-Apr;9(2):126-33
references.pmid: 12784878
references.citation: Genetics. 2005 Sep;171(1):259-67
references.pmid: 15965248
references.citation: Oncogene. 2009 Oct 15;28(41):3642-51
references.pmid: 19648964
references.citation: Nat Genet. 1998 Aug;19(4):361-5
references.pmid: 9697697
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9657-62
references.pmid: 18621709
references.citation: Curr Biol. 2000 Jan 27;10(2):76-85
references.pmid: 10662667
references.citation: J Cell Biol. 2002 Feb 18;156(4):725-36
references.pmid: 11839772
references.citation: Nature. 2007 Aug 16;448(7155):807-10
references.pmid: 17676035
references.citation: Genes Dev. 1996 Mar 15;10(6):659-71
references.pmid: 8598294
references.citation: Exp Cell Res. 1983 Jan;143(1):103-14
references.pmid: 6825714
references.citation: J Cell Biol. 1998 Jan 12;140(1):211-21
references.pmid: 9425168
references.citation: EMBO J. 1994 Aug 15;13(16):3748-56
references.pmid: 8070403
references.citation: J Exp Med. 1996 Oct 1;184(4):1365-75
references.pmid: 8879209
references.citation: Development. 2008 Apr;135(7):1355-64
references.pmid: 18305002
references.citation: J Cell Biol. 1996 Jul;134(1):133-48
references.pmid: 8698810
references.citation: Development. 2005 Jun;132(11):2547-59
references.pmid: 15857910
references.citation: Cell. 1987 Apr 24;49(2):177-84
references.pmid: 3105892
references.citation: J Cell Sci. 1998 Apr;111 ( Pt 8):1071-80
references.pmid: 9512503
references.citation: Mol Cell Biol. 1996 Jul;16(7):3327-37
references.pmid: 8668148
references.citation: Biochem Biophys Res Commun. 1999 Aug 19;262(1):25-30
references.pmid: 10448062
references.citation: Development. 2007 Jun;134(12):2337-47
references.pmid: 17537798
references.citation: Genome Biol. 2007;8(7):R145
references.pmid: 17645804
references.citation: Oncogene. 2010 Aug 5;29(31):4449-59
references.pmid: 20498643
references.citation: Nat Genet. 2004 Mar;36(3):288-92
references.pmid: 14981519
references.citation: Genetics. 2004 Nov;168(3):1477-89
references.pmid: 15579700
references.citation: BMC Cell Biol. 2004 May 16;5:20
references.pmid: 15144564
references.citation: Trends Cell Biol. 2000 Mar;10(3):111-9
references.pmid: 10675905
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9536-41
references.pmid: 16769879
references.citation: J Natl Cancer Inst. 2000 Jan 19;92(2):112-20
references.pmid: 10639512
references.citation: Cancer Res. 2010 May 15;70(10):4054-63
references.pmid: 20442290
references.citation: J Biol Chem. 2004 Jul 9;279(28):29681-90
references.pmid: 15051726
references.citation: Development. 2002 Sep;129(17):3983-94
references.pmid: 12163402
references.citation: Cereb Cortex. 2010 Mar;20(3):661-71
references.pmid: 19587023
references.citation: Cancer Res. 2009 Sep 15;69(18):7198-206
references.pmid: 19738060
references.citation: Cancer Res. 2006 May 1;66(9):4672-80
references.pmid: 16651418
references.citation: Development. 2007 Apr;134(8):1539-48
references.pmid: 17360775
references.citation: J Cell Sci. 2002 Jan 1;115(Pt 1):99-111
references.pmid: 11801728
references.citation: Nat Cell Biol. 2008 Sep;10(9):1027-38
references.pmid: 19160483
references.citation: J Biol Chem. 1997 May 30;272(22):14320-6
references.pmid: 9162067
references.citation: Cell. 2006 Jun 30;125(7):1269-81
references.pmid: 16814714
references.citation: Mol Biol Cell. 2008 Apr;19(4):1627-36
references.pmid: 18256281
references.citation: Cell. 1990 Dec 21;63(6):1167-76
references.pmid: 2261639
references.citation: Development. 1999 Mar;126(6):1327-35
references.pmid: 10021350
references.citation: Trends Cell Biol. 2006 May;16(5):257-63
references.pmid: 16581250
references.citation: Exp Cell Res. 2000 Apr 10;256(1):168-78
references.pmid: 10739664
references.citation: Genetics. 1998 Mar;148(3):1127-42
references.pmid: 9539430
references.citation: J Biol Chem. 1997 Feb 14;272(7):4230-6
references.pmid: 9020138
references.citation: J Cell Biol. 1998 Feb 23;140(4):961-72
references.pmid: 9472046
references.citation: Cell. 2008 Oct 31;135(3):510-23
references.pmid: 18984162
references.citation: Cell Mol Life Sci. 2010 Apr;67(7):1025-48
references.pmid: 19937461
references.citation: Leuk Lymphoma. 1997 Dec;28(1-2):65-72
references.pmid: 9498705
references.citation: Cancer Res. 2007 Oct 1;67(19):8975-9
references.pmid: 17908996
references.citation: J Cell Biol. 2003 Feb 3;160(3):433-49
references.pmid: 12551951