Journal of Clinical Research & Bioethics

REG controls Hippo signaling and reciprocal NF-B-YAP regulation to promote colon cancer

6^th International Conference on Advanced Clinical Research and Clinical Trials

September 10-11, 2018 | Zurich, Switzerland

Xiaotao Li

China

Posters & Accepted Abstracts: J Clin Res Bioeth

Abstract:

Background & Aims: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers closely associated with inflammation and hyperactive growth. We have previously demonstrated a regulatory circuit between the proteasome activator REG??????????????� and NF-kappaB (NF-??????????????�B) during colon inflammation, known to be important in the development of colitis-associated cancer as well as sporadic CRC. This study intends to address that the inflammatory microenvironment affects the Hippo pathway during CRC development via a ubiquitin-independent protein degradation mechanism. Methods: We used molecular, cellular, animal tumor models and human CRC samples to define REG??????????????� as an oncogenic regulator during colorectal cancer development. Results: REG??????????????� can directly interact with Lats1 and promote its degradation, which facilitates Yes-associated protein (YAP) activation in colon cancer cells. REG??????????????� deficiency significantly attenuated colon cancer growth, associated with decreased YAP activity in vitro and in vivo. Furthermore, reciprocal activation of YAP and NF-??????????????�B pathways was observed in human colon cancer cells. REG??????????????� Overexpression was found in over 60% of 172 CRC specimens, highly correlating with the elevation of YAP and p65. Post-operative follow-up revealed a significantly lower survival rate in patients with concomitantly high expression of REG??????????????�, YAP and p-p65. Conclusion: REG??????????????� could be a master regulator during CRC development to promote YAP signaling and reinforce cross-talks between inflammation and growth pathways. Therefore, REG??????????????� appears to be a new marker for prognosis of CRC patients and a potential therapeutic target.

Biography :

E-mail: xiaotaol@bcm.edu