Source: The First Affiliated Hospital
Edited by: Tan Rongyu, Wang Dongmei

Zhang Nu group from The First Affiliated Hospital of Sun Yat-sen University published an article entitled“Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signaling”in Nature Cell Biology on March 4, 2021. The paper revealed that C-E-Cad is one of the key reasons of TKI primary resistance in Glioma stem cells. Targeting C-E-Cad was potential precise therapy strategy.

This paper was finished in cooperation with Professor Shi-Yuan Cheng from Feinberg medical college, Northwest University. Post-doctor Gao Xinya, Li Fanying, Doctor Xia Xin and research assistant Zhang Maolei were listed as first authors. The First Affiliated Hospital of Sun Yat-sen University was the first and the last organization of this article, and this work was finished with the support of Translational Medicine Innovation Platform.

GBM is one of the most common malignancy in Central Nerve system. EGFR was amplificated in almost 50% GBMs. Glioma Stem Cell (GSC) play crucial role in the tumorigenesis, recurrence and chemotherapy resistance. Targeting EGFR was one of the most important targeting strategies in previse therapy.

The results of TKI in clinical trials were disappointing. No effective target therapy was applied in clinical practice. Uncovering the mechanism of EGFR activation was still in urgent demand.

Zhang Nu group analyzed the results of Circ-RNA Seq and ribosome profiling in paired GBM and normal brain tissues. The results showed that circular RNA Circ-E-Cad was upregulated and encoded a protein C-E-Cad. C-E-Cad activated EGFR/EGFRviii through endocrine and paracrine and thus promoted the self-renewal of GSCs. C-E-Cad directly binds with CR2 domain of EGFR/EGFRviii and activated EGFR/EGFRviii in low dosage (Figure 1).


In PDX model, targeting C-E-Cad could prolonged the overall survival. The therapy was better than targeting EGFR and there are synergy effects in combination therapy.

This work was supported in part by the National Natural Science Outstanding Youth Foundation of China (81822033 to N.Z.), the National Key Research and Development Program of China (2016YFA0503000 to N.Z.), the National Natural Science Foundation of China (81572477 and 81772683 to N.Z.).

Link to the paper: https://doi.org/10.1038/s41556-021-00639-4