TY  - JOUR
T1  - Small-Molecule Inhibition of SOST Suppresses Breast Cancer Bone Metastasis
A1  - Yousef Hamdan Khalil
A1  - Omar Salman Nassar
JF  - Archive of International Journal of Cancer and Allied Science
JO  - Arch Int J Cancer Allied Sci
SN  - 3108-4834
Y1  - 2025
VL  - 5
IS  - 1
DO  - 10.51847/XR3tpAzZri
SP  - 1
EP  - 17
N2  - Osteoporosis can worsen breast cancer metastasis to bone, correlates with poor long-term prognosis, and currently has limited treatment options. Sclerostin (SOST), a natural inhibitor of bone formation, represents a promising target for osteoporosis therapy. Nevertheless, it remains uncertain whether SOST could serve as a therapeutic target for breast cancer bone metastases, and if small-molecule agents that modulate SOST in breast cancer cells can suppress bone metastasis. SOST levels were assessed in 442 breast cancer specimens via immunohistochemistry, and statistical analyses were conducted to evaluate the correlation with bone metastasis. Bone-metastatic SCP2 breast cancer cells were subjected to SOST knockdown or overexpression, and their metastatic behaviors in bone were examined both in vitro and in vivo. To explore potential therapeutic strategies, we screened small-molecule inhibitors targeting the SOST-STAT3 interaction and evaluated the anti-tumor and anti-metastatic effects of one lead compound in vitro and in vivo. Elevated SOST expression correlated with breast cancer bone metastasis and poorer patient survival. Knockdown of SOST notably decreased the bone metastatic potential of SCP2 cells. Mechanistically, SOST bound STAT3 to activate TGF-β/KRAS signaling, promoting tumor proliferation and bone metastasis. Administration of the candidate compound, S6, markedly suppressed the growth of breast cancer organoids and bone metastases in murine models. These results identify a novel therapeutic avenue for addressing bone metastasis in breast cancer.
UR  - https://smerpub.com/article/small-molecule-inhibition-of-sost-suppresses-breast-cancer-bone-metastasis-tx8hohr1j4ld9va
ER  -