Xin-Hua Feng
AAAS Fellow
National Distinguished Professor
Zhejiang Distinguished Expert
Zhejiang University Qiushi Chair Professor
Director, Life Sciences Institute, Zhejiang University
Title:
To TGF-b or not to TGF-b, that is the question in cancer and development.
Abstract:
TGF-b, BMPs and related cytokines play essential roles in normal development. In physiological settings, strength and duration of TGF-b signaling are tightly and precisely controlled. I am going to share two stories. The first story is on TGF-b signaling: how tumor cells develop strategies to escape from TGF-b anti-growth control. It has been known that one mechanism to resist the cytostatic effect of TGF-b is through inactivating mutations/deletions of genes in the TGF-bsignaling pathway such as Smad4, which frequently occur in gastrointestinal and pancreatic cancer. However, deletion or mutations in the Smad4 gene are rare in other types of cancers. We have found that TGF-b signaling could be impaired by ALK that phosphorylates Smad4 on tyrosine and inactivates the latter’s tumor suppressor activity. The second story is on BMP signaling: how BMP signaling is attenuated by lysosomal degradation of the BMP type I receptor. an ER-resident LC3-binding protein interacts with the type I BMP receptor (BMPR1) and causes the receptor degradation through the autophagosome, thereby impacting intestinal crypt regeneration. Our novel studies gain molecular insights into TGF-bsuperfamily signaling in development and tumorigenesis.
Date: March 2nd, 2022
Time: 15:30-16:30
Host: Wanlu Liu, Qianting Zhang
