Silencing of the EPHB3 tumor-suppressor gene in human colorectal cancer through decommissioning of a transcriptional enhancer

18.03.2014

Jägle S, Rönsch K, Timme S, Andrlova H, Bertrand M, Jäger M, Proske A, Schrempp M, Yousaf A, Michoel T, Zeiser R, Werner M, Lassmann S, Hecht A

Proc Natl Acad Sci U S A. 2014;111(13):4886-91

Proc Natl Acad Sci U S A.         online article

In colorectal cancer, tissue invasion - the first step towards metastasis - is facilitated by down-regulation of Ephrin type-B receptor tyrosine kinases (EPHB). Our study shows that inactivation of the EPHB3 tumor suppressor gene results from the incapacitation of a transcriptional enhancer element. EPHB3 enhancer dysfunction is a consequence of defective Notch signaling, which undergoes a switch in functional importance and becomes dispensable and even tumor suppressive in the course of tumorigenesis.