| pubmed-article:19147560 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0242957 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0010853 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0001511 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0597357 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0021701 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0069515 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0031727 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0040690 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0004083 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0009085 | lld:lifeskim |
| pubmed-article:19147560 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:19147560 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:19147560 | pubmed:dateCreated | 2009-1-16 | lld:pubmed |
| pubmed-article:19147560 | pubmed:abstractText | It has been proposed that cross talk between integrin and growth factor receptor signaling such as ErbB2 (HER2) is required for activation of downstream effectors and ErbB2-mediated mammary tumorigenesis. Here we show that transforming growth factor beta (TGF-beta) induced focal adhesion kinase (FAK)-dependent clustering of HER2 and integrins alpha(6), beta(1), and beta(4) in HER2-overexpressing mammary epithelial cells without altering the total and surface levels of HER2 receptors. This effect was mediated by ligand-induced epidermal growth factor receptor (EGFR) activation and the subsequent phosphorylation of Src and FAK. We have previously reported that TGF-beta up-regulates EGFR ligand shedding through a mechanism involving the phosphorylation of tumor necrosis factor-alpha-converting enzyme (TACE/ADAM17). Knockdown of TACE, FAK, or integrin alpha(6) by siRNA or inhibition of EGFR or Src by specific inhibitors abrogated TGF-beta-induced receptor clustering and signaling to phosphatidylinositol 3-kinase-Akt. Finally, inhibition of Src-FAK reversed TGF-beta-induced resistance to the therapeutic HER2 inhibitor trastuzumab in HER2-overexpressing breast cancer cells. Taken together, these data suggest that, by activating Src-FAK, TGF-beta integrates ErbB receptor and integrin signaling to induce cell migration and survival during breast cancer progression. | lld:pubmed |
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| pubmed-article:19147560 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19147560 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19147560 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19147560 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19147560 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19147560 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:19147560 | pubmed:issn | 1538-7445 | lld:pubmed |
| pubmed-article:19147560 | pubmed:author | pubmed-author:PozziAmbraA | lld:pubmed |
| pubmed-article:19147560 | pubmed:author | pubmed-author:ArteagaCarlos... | lld:pubmed |
| pubmed-article:19147560 | pubmed:author | pubmed-author:QuarantaVitoV | lld:pubmed |
| pubmed-article:19147560 | pubmed:author | pubmed-author:WangShizhen... | lld:pubmed |
| pubmed-article:19147560 | pubmed:author | pubmed-author:ZentRoyR | lld:pubmed |
| pubmed-article:19147560 | pubmed:author | pubmed-author:XiangBinB | lld:pubmed |
| pubmed-article:19147560 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19147560 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:19147560 | pubmed:volume | 69 | lld:pubmed |
| pubmed-article:19147560 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19147560 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19147560 | pubmed:pagination | 475-82 | lld:pubmed |
| pubmed-article:19147560 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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