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SHP-2 promoting migration and metastasis of MCF-7 with loss of E-cadherin, dephosphorylation of FAK and secretion of MMP-9 induced by IL-1 β in vivo andin vitro

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Abstract

Shp-2, an src homology (SH) two-containing phosphotyrosine phosphatase, appears to be involved in cytoplasmic signaling downstream of a variety of cell surface receptors. It also plays an important role in the control of cell spreading, migration, and cytoskeletal architecture. In our study, abrogation of SHP-2 catalytic activity with a’dominant-negative mutant (SHP-2C>S) displayed an increased number of focal adhesion, high expression of E-cadhenrin and phosphorylation of the focal adhesion kinase (FAK). Interestingly, the cells expressing SHP-2C>S showed reduced IL-1β-stimulated chemotaxis compared with either mock- or SHP-2 wild type-transfected cells. We also found that SHP-2-GFP-transfected cell lines did not express E-cadherin nearly and produced high level of the matrix metalloproteinase MMP-9 in the supernatants. The loss of E-cadherin-mediated adhesion and the increase of MMP-9-induced imgration had been shown to play an important role in the transition of epithelial tumors from a benign to an invasive state. These findings have raised the possibility that SHP-2 can promote the cancer cell to invasion the distant tissues. To determine whether SHP-2 promotes invasion and metastasis, we transfected MCF-7 breast cancer cell lines with SHP-2-GFP, SHP-2C>S-GFP and analyzed the effects of the SHP-2 on cell migration, invasion, and metastasis. β, SHP-2-GFP-transfected cells migrated more efficiently, showed an increased invasion of Matrigel, and adhered less efficiently to monolayers of fibroblast cells. When injected into the abdominal cavity of nude mice, SHP-2-GFP-transfected cells metastasized widely to the lung, kidney, but MCF-7 with SHP-2C>S-GFP was not observed in the these organs. These results demonstrate that SHP-2 promotes invasion and metastasis of MCF-7 with the loss of E-cadherin, the dephosphorylation of FAK and the secretion of MMP-9 induced by IL-1β.

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Abbreviations

BSA:

bovine serum albumin

FAK:

focal adhesion kinase

FBS:

fetal bovine serum

GFP:

green fluorescent protein

IL-1β :

interleukin-1β

MMP-9:

matrix metalloproteinase-9

PBS:

phosphate-buf fered saline

PMSF:

phenylmethylsulfonyl fluoride

SHP-2:

an src homology (SH) 2-containing phosphotyrosine phosphatase

References

  • E Kohn L Liotta (1995) ArticleTitleMoculular insights into cancer invasive strategies for prevention and intervention Cancer Res. 55 1856–1862 Occurrence Handle7728753 Occurrence Handle1:CAS:528:DyaK2MXltlSgtr0%3D

    PubMed  CAS  Google Scholar 

  • S Hirohashi Y Kanai (2003) ArticleTitleCell adhesion system and human cancer morphogenesis Cancer Sci. 94 IssueID7 575–581 Occurrence Handle12841864 Occurrence Handle10.1111/j.1349-7006.2003.tb01485.x Occurrence Handle1:CAS:528:DC%2BD2cXhs1Kgs7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • GS Feng T Pawson (1994) ArticleTitlePhosphotyrosine phosphatases with SH2 domains: regulators of signal transduction Trends Genet 10 IssueID2 54–58 Occurrence Handle8191586 Occurrence Handle10.1016/0168-9525(94)90149-X Occurrence Handle1:CAS:528:DyaK2cXlvF2jsrg%3D

    Article  PubMed  CAS  Google Scholar 

  • K Takenaga (1996) ArticleTitleSuppression of metastatic potential of high-metastatic Lewis lung carcinoma cells by vanadate, an inhibitor of tyrosine phosphatase, through inhibiting cell-substrate adhesion Invasion Metastasis 16 97–106 Occurrence Handle9030244 Occurrence Handle1:CAS:528:DyaK2sXhtlOrtbg%3D

    PubMed  CAS  Google Scholar 

  • D Yu C Qu O Henegariu X Lu G Feng (1998) ArticleTitleProtein-tyrosine phosphatase SHP-2 regulates cell spreading, migration and focal adhesion J Biol Chem 273 21125–21131 Occurrence Handle9694867 Occurrence Handle10.1074/jbc.273.33.21125 Occurrence Handle1:CAS:528:DyaK1cXlsFOrsb0%3D

    Article  PubMed  CAS  Google Scholar 

  • ZZ Zhao ZJ Tan JH Wright CD Diltz SH Shen EG Krebs EH Fischer (1995) ArticleTitleAltered expression of protein-tyrosine phosphatase 2C in 293 cells affects protein tyrosine phosphorylation and mitogen-activated protein kinase activation. J Biol Chem 270 IssueID20 11765–11769 Occurrence Handle7744825 Occurrence Handle10.1074/jbc.270.20.11765 Occurrence Handle1:CAS:528:DyaK2MXlvVWks70%3D

    Article  PubMed  CAS  Google Scholar 

  • S Manes E Mira C Gomez-Mouton ZJ Zhao RA Lacalle C Martinez-A (1999) ArticleTitleConcerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Mol Cell Biol 19 IssueID4 3125–3135 Occurrence Handle10082579 Occurrence Handle1:CAS:528:DyaK1MXit1alu7w%3D

    PubMed  CAS  Google Scholar 

  • G Feng C Hui T Pawson (1993) ArticleTitleSH2-containing phosphotyrosine phosphatases as a target of protein-tyrosine kinases Science 259 1607–1610 Occurrence Handle8096088 Occurrence Handle10.1126/science.8096088 Occurrence Handle1:CAS:528:DyaK3sXktVWlt74%3D

    Article  PubMed  CAS  Google Scholar 

  • W Vogel R Lammers J Huang A Ullrich (1993) ArticleTitleActivation of a phosphotyrosine phosphatase by tyrosine phosphorylation Science 259 1611–1614 Occurrence Handle7681217 Occurrence Handle10.1126/science.7681217 Occurrence Handle1:CAS:528:DyaK3sXktVWlt78%3D

    Article  PubMed  CAS  Google Scholar 

  • M Kuhné T Pawson G Lienhard G Feng (1993) ArticleTitleThe insulin-receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp J Biol Chem 268 11479–11481

    Google Scholar 

  • B Seely D Reichart P Staubs B Juhn D Hsu H Maegawa K Milarski A Saltiel J Olefsky (1995) ArticleTitleLocalization of the insulin-like growth factor I receptor binding sites for the SH2 domain proteins p85, Syp and GTPase activating protein J Biol Chem 270 19151–19157 Occurrence Handle7642582 Occurrence Handle10.1074/jbc.270.32.19151 Occurrence Handle1:CAS:528:DyaK2MXnsVOis7k%3D

    Article  PubMed  CAS  Google Scholar 

  • L Cary J Chang J Guan (1996) ArticleTitleStimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn J Cell Sci 109 1787–1794 Occurrence Handle8832401 Occurrence Handle1:CAS:528:DyaK28XksFCksb8%3D

    PubMed  CAS  Google Scholar 

  • D Ilic Y Furuta S Kanazawa N Takeda K Sobue N Nakatsuji S Nomura J Fujimoto M Okada T Yamamoto S Aizawa (1995) ArticleTitleReduced cell motility and enhanced focal contact formation in cells from FAK-deficient mice Nature 377 539–544 Occurrence Handle1:CAS:528:DyaK2MXoslWltrw%3D Occurrence Handle7566154 Occurrence Handle10.1038/377539a0

    Article  CAS  PubMed  Google Scholar 

  • RK Vadlamudi L Adam D Nguyen M Santos R Kumar (2002) ArticleTitleDifferential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2. J Cell Physiol 190 IssueID2 189–199 Occurrence Handle11807823 Occurrence Handle10.1002/jcp.10054 Occurrence Handle1:CAS:528:DC%2BD38Xjt1CrtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • E Avizienyte AW Wyke RJ Jones GW McLean MA Westhoff VG Brunton MC Frame (2002) ArticleTitleSrc-induced de-regulation of E-cadherin in colon cancer cells requires integrin signaling. Nat Cell Biol 4 IssueID8 632–638 Occurrence Handle12134161 Occurrence Handle1:CAS:528:DC%2BD38Xls1OrtLk%3D

    PubMed  CAS  Google Scholar 

  • DS Goodsell (2002) ArticleTitleThe molecular perspective: cadherin Stem Cells 20 IssueID6 583–584 Occurrence Handle12456966 Occurrence Handle10.1634/stemcells.20-6-583

    Article  PubMed  Google Scholar 

  • UB Hofmann AA Eggert K Blass EB Brocker JC Becker (2003) ArticleTitleExpression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer Res 63 IssueID23 8221–8225 Occurrence Handle14678978 Occurrence Handle1:CAS:528:DC%2BD3sXpvVagtrc%3D

    PubMed  CAS  Google Scholar 

  • SB Kondapaka R Fridman KB Reddy (1997) ArticleTitleEpidermal growth factor and amphiregulin up-regulate matrix metalloproteinase-9 (MMP-9) in human breast cancer cells. Int J Cancer 70 IssueID6 722–726 Occurrence Handle9096655 Occurrence Handle10.1002/(SICI)1097-0215(19970317)70:6<722::AID-IJC15>3.0.CO;2-B Occurrence Handle1:CAS:528:DyaK2sXislaltr8%3D

    Article  PubMed  CAS  Google Scholar 

  • H Knupfer D Stanitz M Brauckhoff R Schmidt MM Knupfer R Preiss (2001) ArticleTitleIL-1 receptor type I expression in breast cancer. Breast 10 IssueID5 411–415 Occurrence Handle14965616 Occurrence Handle10.1054/brst.2000.0269 Occurrence Handle1:STN:280:DC%2BD2c%2Fns1Clsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • X Song E Voronov T Dvorkin E Fima E Cagnano D Benharroch Y Shendler O Bjorkdahl S Segal CA Dinarello RN Apte (2003) ArticleTitleDifferential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness J Immunol. 171 IssueID12 6448–6456 Occurrence Handle14662844 Occurrence Handle1:CAS:528:DC%2BD3sXpsV2rsb8%3D

    PubMed  CAS  Google Scholar 

  • E Eden GM Turino (1986) ArticleTitleInterleukin 1 secretion from human alveolar macrophages in lung disease J Clin Immunol 6 326–333 Occurrence Handle3489003 Occurrence Handle10.1007/BF00917334 Occurrence Handle1:STN:280:BimA3cvos10%3D

    Article  PubMed  CAS  Google Scholar 

  • MO Fagarasan F Aiello K Muegge S Durum J Axelrod (1990) ArticleTitleInterleukin 1 induces beta-endorphin secretion via Fos and Jun in AtT-20 pituitary cells. Proc Natl Acad Sci USA 87 IssueID20 7871–7874 Occurrence Handle1978316 Occurrence Handle10.1073/pnas.87.20.7871 Occurrence Handle1:CAS:528:DyaK3cXmtV2kt7k%3D

    Article  PubMed  CAS  Google Scholar 

  • QA Hamid PJ Reddy M Tewari S Uematsu OC Tuncay DS Tewari (2000) ArticleTitleRegulation of IL-1-induced gingival collagenase gene expression by activator protein-1 (c-Fos/c-Jun). Cytokine 12 IssueID11 1609–1619 Occurrence Handle11052811 Occurrence Handle10.1006/cyto.2000.0676 Occurrence Handle1:CAS:528:DC%2BD3cXnsFaktbg%3D

    Article  PubMed  CAS  Google Scholar 

  • GK Kumkumian R Lafyatis EF Remmers JP Case SJ Kim RL Wilder (1989) ArticleTitlePlatelet-derived growth factor and IL-1 interactions in rheumatoid arthritis. Regulation of synoviocyte proliferation, prostaglandin production, collagenase transcription. J Immunol 143 IssueID3 833–837 Occurrence Handle2545778 Occurrence Handle1:CAS:528:DyaL1MXltFemtr8%3D

    PubMed  CAS  Google Scholar 

  • JP Caron G Tardif J Martel-Pelletier JA DiBattista C Geng JP Pelletier (1996) ArticleTitleModulation of matrix metalloprotease 13 (collagenase 3) gene expression in equine chondrocytes by interleukin 1 and corticosteroids. Am J Vet Res 57 IssueID11 1631–1634 Occurrence Handle8915443 Occurrence Handle1:CAS:528:DyaK28XntV2gtr8%3D

    PubMed  CAS  Google Scholar 

  • M Tsujino Y Hirata T Imai K Kanno S Eguchi H Ito F Marumo (1994) ArticleTitleInduction of nitric oxide synthase gene by interleukin-1 beta in cultured rat cardiocytes Circulation 90 IssueID1 375–383 Occurrence Handle7517798 Occurrence Handle1:CAS:528:DyaK2cXlslOns7o%3D

    PubMed  CAS  Google Scholar 

  • K Kanno Y Hirata T Imai F Marumo (1993) ArticleTitleInduction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells. Hypertension 22 IssueID1 34–39 Occurrence Handle7686532 Occurrence Handle1:CAS:528:DyaK3sXltlOhsLc%3D

    PubMed  CAS  Google Scholar 

  • T Yucel-Lindberg H Ahola J Carlstedt-Duke T Modeer (1999) ArticleTitleInvolvement of tyrosine kinases on cyclooxygenase expression and prostaglandin E2 production in human gingival fibroblasts stimulated with interleukin-1beta and epidermal growth factor. Biochem Biophys Res Commun 257 IssueID2 528–532 Occurrence Handle10198245 Occurrence Handle10.1006/bbrc.1999.0523 Occurrence Handle1:CAS:528:DyaK1MXit1yktL8%3D

    Article  PubMed  CAS  Google Scholar 

  • JA Warner KB Yancey DW MacGlashan SuffixJr (1987) ArticleTitleThe effect of pertussis toxin on mediator release from human basophils J Immunol 139 IssueID1 161–165 Occurrence Handle2438348 Occurrence Handle1:CAS:528:DyaL2sXltFCisrs%3D

    PubMed  CAS  Google Scholar 

  • J Lubinski TC Fong JT Babbitt L Ransone JJ Yodoi ET Bloom (1988) ArticleTitleIncreased binding of IL-2 and increased IL-2 receptor mRNA synthesis are expressed by an NK-like cell line in response to IL-1. J Immunol 140 IssueID6 1903–1909 Occurrence Handle2831272 Occurrence Handle1:CAS:528:DyaL1cXhvVCru7s%3D

    PubMed  CAS  Google Scholar 

  • WB van den Berg (1999) ArticleTitleThe role of cytokines and growth factors in cartilage destruction in osteoarthritis and rheumatoid arthritis. Z Rheumatol 58 IssueID3 136–141 Occurrence Handle10441840 Occurrence Handle10.1007/s003930050163 Occurrence Handle1:CAS:528:DyaK1MXlt1WqtLg%3D

    Article  PubMed  CAS  Google Scholar 

  • J Honig C Rordorf-Adam C Siegmund W Wiedemann F Erard (1989) ArticleTitleIncreased interleukin-1 beta (IL-1 beta) concentration in gingival tissue from periodontitis patients J Periodontal Res. 24 IssueID6 362–367 Occurrence Handle2531790 Occurrence Handle10.1111/j.1600-0765.1989.tb00883.x Occurrence Handle1:STN:280:By%2BD2sbnt1w%3D

    Article  PubMed  CAS  Google Scholar 

  • SA Greenfeder P Nunes L Kwee M Labow RA Chizzonite G Ju (1995) ArticleTitleMolecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J Biol Chem 270 IssueID23 13757–13765 Occurrence Handle7775431 Occurrence Handle10.1074/jbc.270.23.13757 Occurrence Handle1:CAS:528:DyaK2MXmt1yqs70%3D

    Article  PubMed  CAS  Google Scholar 

  • H Wesche K Resch MU Martin (1998) ArticleTitleEffects of IL-1 receptor accessory protein on IL-1 binding FEBS Lett. 429 IssueID3 303–306 Occurrence Handle9662437 Occurrence Handle10.1016/S0014-5793(98)00468-2 Occurrence Handle1:CAS:528:DyaK1cXjvFOiu78%3D

    Article  PubMed  CAS  Google Scholar 

  • B Kimberly M Fabio E Christoph (1998) ArticleTitleMyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem 273 IssueID20 12203–12209 Occurrence Handle1:CAS:528:DyaK1cXjtlSgtro%3D Occurrence Handle9575168 Occurrence Handle10.1074/jbc.273.20.12203

    Article  CAS  PubMed  Google Scholar 

  • K Burns J Clatworthy L Martin (2000) ArticleTitleTollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor Nat Cell Biol. 2 IssueID6 346–351 Occurrence Handle10854325 Occurrence Handle10.1038/35014038 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Sls7k%3D

    Article  PubMed  CAS  Google Scholar 

  • Z Cao WJ Henzel X Gao (1996) ArticleTitleA kinase associated with the interleukin-1 receptor Science 5252 1128–1131 Occurrence Handle10.1126/science.271.5252.1128

    Article  Google Scholar 

  • H Wesche X Gao X Li CJ Kirschning GR Stark Z Cao (1999) ArticleTitleIRAK-M is a novel member of the pelle/interleukin-1 receptor-associated kinase (IRAK) Family. J Biol Chem 27 IssueID274 19403–19410 Occurrence Handle10.1074/jbc.274.27.19403

    Article  Google Scholar 

  • L Aravind VM Dixit EV Koonin (2001) ArticleTitleApoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons. Science 291 1279–1284 Occurrence Handle11181990 Occurrence Handle10.1126/science.291.5507.1279 Occurrence Handle1:CAS:528:DC%2BD3MXhtlSgs74%3D

    Article  PubMed  CAS  Google Scholar 

  • S Li A Strelow EJ Fontana H Wesche (2002) ArticleTitleIRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase Proc Natl Acad Sci USA 99 5567–5572 Occurrence Handle1:CAS:528:DC%2BD38XjtFKlt7s%3D Occurrence Handle11960013 Occurrence Handle10.1073/pnas.082100399

    Article  CAS  PubMed  Google Scholar 

  • PD Arora J Ma W Min T Cruz CA McCulloch (1995) ArticleTitleInterleukin-1-induced calcium flux in human fibroblasts is mediated through focal adhesions J Biol Chem 270 6042–6049 Occurrence Handle7890736 Occurrence Handle10.1074/jbc.270.11.6042 Occurrence Handle1:CAS:528:DyaK2MXksVCntLc%3D

    Article  PubMed  CAS  Google Scholar 

  • EE Qwarnstrom SA MacFarlane RC Page SK Dower (1991) ArticleTitleInterleukin 1ß induces rapid phosphorylation and redistribution of talin: a possible mechanism for modulation of fibroblast focal adhesion Proc Natl Acad Sci USA 88 1232–1236 Occurrence Handle1899925 Occurrence Handle10.1073/pnas.88.4.1232 Occurrence Handle1:CAS:528:DyaK3MXhsVWhtLY%3D

    Article  PubMed  CAS  Google Scholar 

  • YY Lo L Luo CA McCulloch TF Cruz (1998) ArticleTitleRequirements of focal adhesions and calcium fluxes for interleukin-1-induced ERK kinase activation and c-fos expression in fibroblasts J Biol Chem 273 7059–7065 Occurrence Handle9507015 Occurrence Handle10.1074/jbc.273.12.7059 Occurrence Handle1:CAS:528:DyaK1cXitVGgs78%3D

    Article  PubMed  CAS  Google Scholar 

  • SD Ahmad Z Hanville (1993) ArticleTitleA widely expressed human protein-tyrosine phosphatase containing src homology 2 domains Proc Natl Acad Sci 90 2197–2201 Occurrence Handle7681589 Occurrence Handle10.1073/pnas.90.6.2197 Occurrence Handle1:CAS:528:DyaK3sXkt1elsr0%3D

    Article  PubMed  CAS  Google Scholar 

  • KB Kaplan JR Swedlow DO Morgan HE Varmus (1995) ArticleTitlec-Src enhances the spreading of src-/- fibroblasts on fibronectin by a kinase-independent mechanism Genes Dev 9 1505–1517 Occurrence Handle7541382 Occurrence Handle10.1101/gad.9.12.1505 Occurrence Handle1:CAS:528:DyaK2MXms1equr0%3D

    Article  PubMed  CAS  Google Scholar 

  • Z Zhang AO Morla K Vuori JS Bauer RL Juliano E Ruoslahti (1993) ArticleTitleThe alpha v beta 1 integrin functions as a fibronectin receptor but does not support fibronectin matrix assembly and cell migration on fibronectin J Cell Biol 122 235–242 Occurrence Handle8314844 Occurrence Handle10.1083/jcb.122.1.235 Occurrence Handle1:CAS:528:DyaK3sXkvFaitbY%3D

    Article  PubMed  CAS  Google Scholar 

  • I Kenjiro N Tetsuya M Takashi H Tatsuya (2000) ArticleTitleRoles for the protein tyrosine phosphatase SHP-2 in cytoskeletal organization, cell adhesion and cell migration revealed by overexpression of a domain negative mutant Oncogene 19 75–84 Occurrence Handle10.1038/sj.onc.1203204

    Article  Google Scholar 

  • BH Rachel RP Greg FQ Rui (2000) ArticleTitleExogenous expression of N-cadherin in breast cancer cells induces cell migration, invision, metastasis J Cell Biol 148 779–790 Occurrence Handle10.1083/jcb.148.4.779 Occurrence Handle1:CAS:528:DC%2BD3cXhsVOqsLw%3D Occurrence Handle10684258

    Article  CAS  PubMed  Google Scholar 

  • P Doherty LH Rowett SE Moore DA Mann FS Walsh (1991) ArticleTitleNeurite outgrowth in response to transfected N-CAM and N-cadherin reveals fundamental differences in neuronal responsiveness to CAMs Neuron 6 247–258 Occurrence Handle1993122 Occurrence Handle10.1016/0896-6273(91)90360-C Occurrence Handle1:CAS:528:DyaK3MXhs1Wls7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • F Kern S McLeskey L Ahang J Kurebayashi Y Liu I Ding S Kharbanda D Chen D Miller K Cullen S Paik R Dickson (1994) ArticleTitleTransfected MCF-7 cells as a model for breast cancer progression Breast Cancer Res Treat 31 153–165 Occurrence Handle7881095 Occurrence Handle10.1007/BF00666149 Occurrence Handle1:CAS:528:DyaK2MXit1altbg%3D

    Article  PubMed  CAS  Google Scholar 

  • JE Price (1996) ArticleTitleMetastasis from human breast cancer cell lines Breast Cancer Res Treat 39 93–102 Occurrence Handle8738609 Occurrence Handle10.1007/BF01806081 Occurrence Handle1:STN:280:BymA38josFY%3D

    Article  PubMed  CAS  Google Scholar 

  • MJ Wheelock KR Johnson (2003) ArticleTitleCadherins as modulators of cellular phenotype Annu Rev Cell Dev Biol. 19 207–235 Occurrence Handle14570569 Occurrence Handle10.1146/annurev.cellbio.19.011102.111135 Occurrence Handle1:CAS:528:DC%2BD3sXpsFamtrc%3D

    Article  PubMed  CAS  Google Scholar 

  • D Sarrio B Perez-Mies D Hardisson G Moreno-Bueno A Suarez A Cano J Martin-Perez C Gamallo J Palacios (2004) ArticleTitleCytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions Oncogene. 23 IssueID19 3272–3283 Occurrence Handle15077190 Occurrence Handle10.1038/sj.onc.1207439 Occurrence Handle1:CAS:528:DC%2BD2cXjtlChu70%3D

    Article  PubMed  CAS  Google Scholar 

  • A Kodama T Matozakix M Shinohara A Fukuhara K Tachibana M Ichihashi H Nakanishi Y Takai (2001) ArticleTitleRegulation of Ras and Rho small G proteins by SHP-2 Genes Cells. 6 IssueID10 869–876 Occurrence Handle11683915 Occurrence Handle10.1046/j.1365-2443.2001.00467.x Occurrence Handle1:CAS:528:DC%2BD3MXotlCmur4%3D

    Article  PubMed  CAS  Google Scholar 

  • E Rosivatz I Becker K Specht E Fricke B Luber R Busch H Hofler KF Becker (2002) ArticleTitleDifferential expression of the epithelial-mesenchymal transition regulators snail, SIP1, twist in gastric cancer. Am J Pathol 161 IssueID5 1881–1891 Occurrence Handle12414534 Occurrence Handle1:CAS:528:DC%2BD38XptV2gtbk%3D

    PubMed  CAS  Google Scholar 

  • CR Hauck DA Hsia DD Schlaepfer (2002) ArticleTitleThe focal adhesion kinase–a regulator of cell migration and invasion IUBMB Life 53 IssueID2 115–119 Occurrence Handle12049193 Occurrence Handle10.1080/15216540211470 Occurrence Handle1:CAS:528:DC%2BD38XktlGisLo%3D

    Article  PubMed  CAS  Google Scholar 

  • C Morelli K Campioni C Parolin G Palu M Tognon (2004) ArticleTitleActivity of the matrix metalloproteinase-9 promoter in human normal and tumor cells. J Cell Physiol 199 IssueID1 126–133 Occurrence Handle14978741 Occurrence Handle10.1002/jcp.10450 Occurrence Handle1:CAS:528:DC%2BD2cXhs1Sksbw%3D

    Article  PubMed  CAS  Google Scholar 

  • M You LM Flick D Yu GS Feng (2001) ArticleTitleModulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. J Exp Med 193 IssueID1 101–110 Occurrence Handle11136824 Occurrence Handle10.1084/jem.193.1.101 Occurrence Handle1:CAS:528:DC%2BD3MXjtVSgsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • LM Coussens Z Werb (2002) ArticleTitleInflammation and cancer Nature 420 IssueID6917 860–867 Occurrence Handle10.1038/nature01322 Occurrence Handle1:CAS:528:DC%2BD38XpsFygtb4%3D Occurrence Handle12490959

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Embryology and Histology, Second Military Medical University, Shanghai, P.R. China

    Feng-mei Wang, Hou-qi Liu, Shan-rong Liu, Shu-ping Tang & Ling Yang

  2. Burnham Institute, San Diego, CA, USA

    Gen-sheng Feng

  3. Department of Embryology and Histology, Second Military Medical University, Xiangyin Road 800, 200433, Shanghai, P.R. China

    Hou-qi Liu

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  1. Feng-mei Wang
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Correspondence to Hou-qi Liu.

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Wang, Fm., Liu, Hq., Liu, Sr. et al. SHP-2 promoting migration and metastasis of MCF-7 with loss of E-cadherin, dephosphorylation of FAK and secretion of MMP-9 induced by IL-1 β in vivo andin vitro . Breast Cancer Res Treat 89, 5–14 (2005). https://doi.org/10.1007/s10549-004-1002-z

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