Research ArticleCancer

β1 Integrin Inhibition Elicits a Prometastatic Switch Through the TGFβ–miR-200–ZEB Network in E-Cadherin–Positive Triple-Negative Breast Cancer

Sci. Signal.  11 Feb 2014:
Vol. 7, Issue 312, pp. ra15
DOI: 10.1126/scisignal.2004751

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When Treatment Promotes Metastasis

In cancer, therapy aims to kill the primary tumor and prevent metastasis. Truong et al. found that although strategies blocking β1 integrin are effective at treating primary breast tumors, they may cause metastatic disease in certain patients. In E-cadherin–positive triple-negative breast cancer (TNBC) cell lines, blocking β1 integrin function by gene silencing or with antibodies induced epithelial-to-mesenchymal transition (EMT)–associated signaling and the loss of E-cadherin, enabling TNBC cells to migrate individually and invade a three-dimensional collagen matrix in culture. When injected into zebrafish, the β1 integrin–deficient cells disseminated further than the parent TNBC cells. When implanted in mice, these cells formed more lung metastases, despite producing smaller primary tumors compared with those produced by implanted parent cells. Thus, therapies targeted against β1 integrin may not be suitable for some TNBC patients.