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Activation of the MKL1/actin signaling pathway induces hormonal escape in estrogen-responsive breast cancer cell lines.

Abstract : Estrogen receptor alpha (ERα) is generally considered to be a good prognostic marker because almost 70% of ERα-positive tumors respond to anti-hormone therapies. Unfortunately, during cancer progression, mammary tumors can escape from estrogen control, resulting in resistance to treatment. In this study, we demonstrate that activation of the actin/megakaryoblastic leukemia 1 (MKL1) signaling pathway promotes the hormonal escape of estrogen-sensitive breast cancer cell lines. The actin/MKL1 signaling pathway is silenced in differentiated ERα-positive breast cancer MCF-7 and T47D cell lines and active in ERα-negative HMT-3522 T4-2 and MDA-MB-231 breast cancer cells, which have undergone epithelial-mesenchymal transition. We showed that MKL1 activation in MCF-7 cells, either by modulating actin dynamics or using MKL1 mutants, down-regulates ERα expression and abolishes E2-dependent cell growth. Interestingly, the constitutively active form of MKL1 represses PR and HER2 expression in these cells and increases the expression of HB-EGF, TGFβ, and amphiregulin growth factors in an E2-independent manner. The resulting expression profile (ER-, PR-, HER2-) typically corresponds to the triple-negative breast cancer expression profile.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061363
Contributor : Laurent Jonchère <>
Submitted on : Friday, September 5, 2014 - 3:38:20 PM
Last modification on : Wednesday, October 14, 2020 - 4:03:35 AM

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Gwenneg Kerdivel, Antoine Boudot, Denis Habauzit, Frederic Percevault, Florence Demay, et al.. Activation of the MKL1/actin signaling pathway induces hormonal escape in estrogen-responsive breast cancer cell lines.. Molecular and Cellular Endocrinology, Elsevier, 2014, 390 (1-2), pp.34-44. ⟨10.1016/j.mce.2014.03.009⟩. ⟨hal-01061363⟩

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