SOSTDC1

SOSTDC1, also known as Ectodermal BMP inhibitor, Ectodin, Uterine sensitization-associated gene 1 protein, and USAG-1, is a secreted protein encoded by the SOSTDC1 gene. It is a member of the sclerostin family and contains a cysteine knot-like domain and two N-linked glycosylation sites. SOSTDC1 acts as an antagonist of bone morphogenetic proteins (BMPs) by directly binding to BMPs and preventing their interaction with receptors, thereby regulating BMP signaling. It also interacts with LRP6, affecting Wnt signaling, and consequently regulating cell proliferation, differentiation, and programmed cell death.

SOSTDC1 plays various roles in skin, intestine, brain, lung, kidney, and the vascular system. In the skeletal system, SOSTDC1 is critical for bone metabolism, bone density maintenance, and fracture healing. Additionally, the expression of SOSTDC1 is closely related to the development and progression of various types of cancer, including breast cancer, renal cancer, gastric cancer, and thyroid cancer. In triple-negative breast cancer, nuclear translocation of SOSTDC1 was found to enhance the maintenance of stemness in tumor-initiating cells and resistance to the PARP inhibitor Olaparib, providing a new effective target for targeting tumor cells and tumor-initiating cells, which could improve the therapeutic efficacy of PARP inhibitors in triple-negative breast cancer.