Endometrial carcinoma may favor partial, but not complete, loss of the TGF-β signaling pathway

The TGF-β signaling pathway is involved in the development of many types of cancer. In two recent PNAS papers, Montsivais et al. (1) and Kriseman et al. (2) of the Matzuk laboratory investigate the role of the TGF-β signaling pathway in endometrial carcinoma by using gene knockout mouse models. They find that either uterine conditional inactivation of TGF-β receptor Alk5 (1) or uterine double-conditional inactivation of Smad2 and Smad3 (2), which are transcription factors downstream of the receptor, leads to the development of estrogen-dependent metastatic endometrial cancer. They suggest that the TGF-β signaling pathway may serve as an important tumor suppressor in the uterus. These findings significantly advance our understanding of endometrial carcinoma and open novel avenues for future therapeutic strategies. We are particularly interested in the phenotype difference in these two mouse … [↵][1]1To whom correspondence should be addressed. Email: jilongliu{at}scau.edu.cn. [1]: #xref-corresp-1-1