Breast cancer stem-like cells are sensitized to tamoxifen induction of self-renewal inhibition with enforced Let-7c dependent on Wnt blocking

Sun,Xin; Xu,Chongwen; Xiao,Guodong; Meng,Jinying; Wang,Jichang; Tang,Shou‑Ching; Qin,Sida; Du,Ning; Li,Gang; Ren,Hong; Liu,Dapeng

doi:10.3892/ijmm.2018.3388

Breast cancer stem-like cells are sensitized to tamoxifen induction of self-renewal inhibition with enforced Let-7c dependent on Wnt blocking

Authors:
- Xin Sun
- Chongwen Xu
- Guodong Xiao
- Jinying Meng
- Jichang Wang
- Shou‑Ching Tang
- Sida Qin
- Ning Du
- Gang Li
- Hong Ren
- Dapeng Liu
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Affiliations: Department of Thoracic Surgery and Oncology, The Second Department of Thoracic Surgery, Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Otorhinolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Surgery Oncology, The First People's Hospital of Xianyang City, Xianyang, Shaanxi 712000, P.R. China, Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Solid Tumor Clinical Trials, Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Published online on: January 15, 2018 https://doi.org/10.3892/ijmm.2018.3388
Pages: 1967-1975
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Let-7 microRNAs have been reported to have tumor suppressive functions; however, the effect of Let-7 when used in combination with chemotherapies is uncertain, but may have potential for use in clinical practice. In this study, we used RT-qPCR, western blot analysis, cell proliferation assay, flow cytometry analysis, immunohistochemistry (IHC) staining, luciferase assays, cell sorting analysis and xenografted tumor model to explore the role of Let-7 in the chemotherapy sensitivity of breast cancer stem cells. The findings of the current study indicated that Let‑7 enhances the effects of endocrine therapy potentially by regulating the self‑renewal of cancer stem cells. Let‑7c increased the anticancer functions of tamoxifen and reduced the ratio of cancer stem‑like cells (CSCs), sensitizing cells to therapy-induced repression in an estrogen receptor (ER)‑dependent manner. Notably, Let‑7 decreased the tumor formation ability of estrogen‑treated breast CSCs in vivo and suppressed Wnt signaling, which further consolidated the previously hypothesis that Let‑7 decreases the self‑renewal ability, contributing to reduced tumor formation ability of stem cells. The suppressive effects exerted by Let‑7 on stem‑like cells involved Let‑7c/ER/Wnt signaling, and the functions of Let‑7c exerted with tamoxifen were dependent on ER. Taken together, the findings identified a biochemical and functional link between Let‑7 and endocrine therapy in breast CSCs, which may facilitate clinical treatment in the future using delivery of suppressive Let-7.

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