Sun, L., Zhang, Y., Chen, G., Ji, Y., Ma, Q., Qiao, X., Wu, S., Zhou, L., Bu, J., Zhu, X., Zhang, X., Jiang, X., Liu, C., Li, X., Liu, Y., Yang, Y., & Liu, C. (2022). Targeting SOST using a small-molecule compound retards breast cancer bone metastasis. Molecular Cancer, 21(1), Article 228. https://doi.org/10.1186/s12943-022-01697-4
Sun, Lisha ; Zhang, Yixiao ; Chen, Guanglei et al. / Targeting SOST using a small-molecule compound retards breast cancer bone metastasis. In: Molecular Cancer. 2022 ; Vol. 21, No. 1.
@article{e73f0552f8354ca9ae6ece7775670dcb,
title = "Targeting SOST using a small-molecule compound retards breast cancer bone metastasis",
abstract = "Background: Breast cancer metastasis to the bone can be exacerbated by osteoporosis, is associated with poor long-term survival, and has limited therapeutic options. Sclerostin (SOST) is an endogenous inhibitor of bone formation, and an attractive target for treatment of osteoporosis. However, it is unclear whether SOST can be used as a therapeutic target for bone metastases of breast cancer, and whether small molecule compounds that target SOST in breast cancer cells can inhibit breast cancer bone metastasis. Methods: SOST expression in 442 breast cancer tissues was characterized by immunohistochemistry and statistically analyzed for the association with breast cancer bone metastases. Bone metastatic breast cancer SCP2 cells were induced for SOST silencing or overexpression and their bone metastatic behaviors were tested in vitro and in vivo. To identify potential therapeutics, we screened inhibitors of the interaction of SOST with STAT3 from a small chemical molecule library and tested the inhibitory effects of one inhibitor on breast cancer growth and bone metastasis in vitro and in vivo. Results: We found that up-regulated SOST expression was associated with breast cancer bone metastases and worse survival of breast cancer patients. SOST silencing significantly reduced the bone metastatic capacity of SCP2 cells. SOST interacted with STAT3 to enhance the TGF-β/KRAS signaling, increasing both tumor growth and bone metastasis. Treatment with one lead candidate, S6, significantly inhibited the growth of breast-cancer organoids and bone metastasis in mice. Conclusions: Our findings highlight a new class of potential therapeutics for treatment of bone metastasis in breast cancer.",
keywords = "Bone metastasis, Breast cancer, SOST, Small-molecule compound",
author = "Lisha Sun and Yixiao Zhang and Guanglei Chen and Yaoting Ji and Qingtian Ma and Xinbo Qiao and Sijin Wu and Lin Zhou and Jiawen Bu and Xudong Zhu and Xiaoying Zhang and Xiaofan Jiang and Chao Liu and Xinnan Li and Yang Liu and Yongliang Yang and Caigang Liu",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1186/s12943-022-01697-4",
language = "English",
volume = "21",
journal = "Molecular Cancer",
issn = "1476-4598",
number = "1",
}
Sun, L, Zhang, Y, Chen, G, Ji, Y, Ma, Q, Qiao, X, Wu, S, Zhou, L, Bu, J, Zhu, X, Zhang, X, Jiang, X, Liu, C, Li, X, Liu, Y, Yang, Y & Liu, C 2022, 'Targeting SOST using a small-molecule compound retards breast cancer bone metastasis', Molecular Cancer, vol. 21, no. 1, 228. https://doi.org/10.1186/s12943-022-01697-4
Targeting SOST using a small-molecule compound retards breast cancer bone metastasis. / Sun, Lisha; Zhang, Yixiao; Chen, Guanglei et al.
In:
Molecular Cancer, Vol. 21, No. 1, 228, 12.2022.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Targeting SOST using a small-molecule compound retards breast cancer bone metastasis
AU - Sun, Lisha
AU - Zhang, Yixiao
AU - Chen, Guanglei
AU - Ji, Yaoting
AU - Ma, Qingtian
AU - Qiao, Xinbo
AU - Wu, Sijin
AU - Zhou, Lin
AU - Bu, Jiawen
AU - Zhu, Xudong
AU - Zhang, Xiaoying
AU - Jiang, Xiaofan
AU - Liu, Chao
AU - Li, Xinnan
AU - Liu, Yang
AU - Yang, Yongliang
AU - Liu, Caigang
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Breast cancer metastasis to the bone can be exacerbated by osteoporosis, is associated with poor long-term survival, and has limited therapeutic options. Sclerostin (SOST) is an endogenous inhibitor of bone formation, and an attractive target for treatment of osteoporosis. However, it is unclear whether SOST can be used as a therapeutic target for bone metastases of breast cancer, and whether small molecule compounds that target SOST in breast cancer cells can inhibit breast cancer bone metastasis. Methods: SOST expression in 442 breast cancer tissues was characterized by immunohistochemistry and statistically analyzed for the association with breast cancer bone metastases. Bone metastatic breast cancer SCP2 cells were induced for SOST silencing or overexpression and their bone metastatic behaviors were tested in vitro and in vivo. To identify potential therapeutics, we screened inhibitors of the interaction of SOST with STAT3 from a small chemical molecule library and tested the inhibitory effects of one inhibitor on breast cancer growth and bone metastasis in vitro and in vivo. Results: We found that up-regulated SOST expression was associated with breast cancer bone metastases and worse survival of breast cancer patients. SOST silencing significantly reduced the bone metastatic capacity of SCP2 cells. SOST interacted with STAT3 to enhance the TGF-β/KRAS signaling, increasing both tumor growth and bone metastasis. Treatment with one lead candidate, S6, significantly inhibited the growth of breast-cancer organoids and bone metastasis in mice. Conclusions: Our findings highlight a new class of potential therapeutics for treatment of bone metastasis in breast cancer.
AB - Background: Breast cancer metastasis to the bone can be exacerbated by osteoporosis, is associated with poor long-term survival, and has limited therapeutic options. Sclerostin (SOST) is an endogenous inhibitor of bone formation, and an attractive target for treatment of osteoporosis. However, it is unclear whether SOST can be used as a therapeutic target for bone metastases of breast cancer, and whether small molecule compounds that target SOST in breast cancer cells can inhibit breast cancer bone metastasis. Methods: SOST expression in 442 breast cancer tissues was characterized by immunohistochemistry and statistically analyzed for the association with breast cancer bone metastases. Bone metastatic breast cancer SCP2 cells were induced for SOST silencing or overexpression and their bone metastatic behaviors were tested in vitro and in vivo. To identify potential therapeutics, we screened inhibitors of the interaction of SOST with STAT3 from a small chemical molecule library and tested the inhibitory effects of one inhibitor on breast cancer growth and bone metastasis in vitro and in vivo. Results: We found that up-regulated SOST expression was associated with breast cancer bone metastases and worse survival of breast cancer patients. SOST silencing significantly reduced the bone metastatic capacity of SCP2 cells. SOST interacted with STAT3 to enhance the TGF-β/KRAS signaling, increasing both tumor growth and bone metastasis. Treatment with one lead candidate, S6, significantly inhibited the growth of breast-cancer organoids and bone metastasis in mice. Conclusions: Our findings highlight a new class of potential therapeutics for treatment of bone metastasis in breast cancer.
KW - Bone metastasis
KW - Breast cancer
KW - SOST
KW - Small-molecule compound
UR - http://www.scopus.com/inward/record.url?scp=85145119980&partnerID=8YFLogxK
U2 - 10.1186/s12943-022-01697-4
DO - 10.1186/s12943-022-01697-4
M3 - Article
C2 - 36581888
AN - SCOPUS:85145119980
SN - 1476-4598
VL - 21
JO - Molecular Cancer
JF - Molecular Cancer
IS - 1
M1 - 228
ER -
Sun L, Zhang Y, Chen G, Ji Y, Ma Q, Qiao X et al. Targeting SOST using a small-molecule compound retards breast cancer bone metastasis. Molecular Cancer. 2022 Dec;21(1):228. doi: 10.1186/s12943-022-01697-4
