Fatima Iram, Barman Susmita, Rai Rajani, Thiel Kristina W W, Chandra Vishal
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Division of Endocrinology, Central Drug Research Institute, Uttar Pradesh, Lucknow 226031, India.
Cancers (Basel). 2021 May 13;13(10):2351. doi: 10.3390/cancers13102351.
This review presents new findings on Wnt signaling in endometrial carcinoma and implications for possible future treatments. The Wnt proteins are essential mediators in cell signaling during vertebrate embryo development. Recent biochemical and genetic studies have provided significant insight into Wnt signaling, in particular in cell cycle regulation, inflammation, and cancer. The role of Wnt signaling is well established in gastrointestinal and breast cancers, but its function in gynecologic cancers, especially in endometrial cancers, has not been well elucidated. Development of a subset of endometrial carcinomas has been attributed to activation of the APC/β-catenin signaling pathway (due to β-catenin mutations) and downregulation of Wnt antagonists by epigenetic silencing. The Wnt pathway also appears to be linked to estrogen and progesterone, and new findings implicate it in mTOR and Hedgehog signaling. Therapeutic interference of Wnt signaling remains a significant challenge. Herein, we discuss the Wnt-activating mechanisms in endometrial cancer and review the current advances and challenges in drug discovery.
本综述介绍了子宫内膜癌中Wnt信号传导的新发现及其对未来可能治疗方法的启示。Wnt蛋白是脊椎动物胚胎发育过程中细胞信号传导的重要介质。最近的生化和遗传学研究为Wnt信号传导提供了重要见解，特别是在细胞周期调控、炎症和癌症方面。Wnt信号传导在胃肠道癌和乳腺癌中的作用已得到充分证实，但其在妇科癌症，尤其是子宫内膜癌中的功能尚未得到充分阐明。一部分子宫内膜癌的发生归因于APC/β-连环蛋白信号通路的激活（由于β-连环蛋白突变）以及通过表观遗传沉默导致Wnt拮抗剂的下调。Wnt通路似乎也与雌激素和孕激素有关，新的发现表明它与mTOR和Hedgehog信号传导有关。对Wnt信号传导的治疗干预仍然是一项重大挑战。在此，我们讨论子宫内膜癌中Wnt激活机制，并综述药物发现的当前进展和挑战。
