Bone morphogenetic protein signaling is a possible therapeutic target in gynecologic cancer. Issue 3 (16th December 2022)

• Record Type: Journal Article
• Authors: Fukuda, Tomohiko; Suzuki, Eri; Fukuda, Risa
• Is Part Of: Cancer science. Volume 114:Issue 3(2023)
• Page Start: 722
• Page End: 729
• Publication Date: 2022-12-16
• Subjects: bone morphogenetic protein -- cancer stem cell -- chemoresistance -- epithelial–mesenchymal transition -- gynecologic cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15682
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily. BMPs play crucial roles in embryogenesis and bone remodeling. Recently, BMP signaling has been found to have diverse effects on different types of tumors. In this review, we summarized the effects of BMP signaling on gynecologic cancer. BMP signaling has tumor‐promoting effects on ovarian cancer (OC) and endometrial cancer (EC), whereas it has tumor‐suppressing effects on uterine cervical cancer (UCC). Interestingly, EC has frequent gain‐of‐function mutations in ACVR1, encoding one of the type I BMP receptors, which are also observed in fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. Little is known about the relationship between BMP signaling and other gynecologic cancers. Tumor‐promoting effects of BMP signaling in OC and EC are dependent on the promotion of cancer stemness and epithelial–mesenchymal transition (EMT). In accordance, BMP receptor kinase inhibitors suppress the cell growth and migration of OC and EC. Since both cancer stemness and EMT are associated with chemoresistance, BMP signaling activation might also be an important mechanism by which OC and EC patients acquire chemoresistance. Therefore, BMP inhibitors are promising for OC and EC patients even if they become resistant to standard chemotherapy. In contrast, BMP signaling inhibits UCC growth in vitro. However, the in vivo effects of BMP signaling have not been elucidated in UCC. In conclusion, BMP signaling has a variety of functions, depending on the types of gynecologic cancer. Therefore, targeting BMP signaling should improve the treatment of patients with gynecologic cancer. Abstract : Bone morphogenetic protein (BMP) secretion from cancer cells and carcinoma‐associated mesenchymal stem cells (CA‐MSCs) is triggered by chemotherapy and cancer‐secreted Hedgehog, respectively. Once secreted, BMP ligands enhance cancer proliferation and stemness via c‐KIT induction and also trigger EMT through SNAIL/SLUG induction, leading to the enhancement of migration and invasion. These effects are partially attributed to FN14 induction.