Survival of cancer cell in maintained by EGFR independent of its kinase activity (Cancer Cell, 2008, 13:385-393)

報告日期: 2008/10/24
報告時間: 15:10/16:00
報告學生: 馬志遠(英文報告)
講評老師: 陳炳焜

Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity

Zhang Weihua, Rachel Tsan, Wei-Chien Huang, Qiuyu Wu, Chao-Hua Chiu, Isaiah J. Fidler, and Mien-Chie Hung

Cancer Cell 13, 385-393 (2008).


Speaker: Chih-Yuan Ma

Commentator: Ben-Kuen Chen, Ph.D.

Date: 2008.10.24 (15:10-16:00)

Room: 602



Epidermal growth factor receptor (EGFR) is a well-characterized member of receptor tyrosine kinase family and highly expresses in many tumors of epithelial origin. EGFR kinase activity triggers numerous downstream signaling pathways to regulate cell proliferation and survival. Inhibition of EGFR kinase activity by tyrosine kinase inhibitors have been served as attractive drugs for cancer treatment. However, the response rates are very low in clinical treatment. In this study, authors observed that knockdown of EGFR by siRNA in cancer cells leads to cell death, whereas inhibition of EGFR kinase activity by tyrosine kinase inhibitors decreases cell proliferation but not cell death. In addition, knockdown of EGFR reduces intracellular glucose level in cancer cells, but inhibition of EGFR kinase activity does not. Glucose is transported into cells by facilitative-type glucose transporter family (GLUT) and active-type glucose transporter family (sodium/glucose cotransporter [SGLT]). Knockdown of EGFR decreases SGLT1 protein level but not mRNA level, and EGFR can interact with SGLT1 without EGFR kinase activity. This indicated that EGFR not only interacts with SGLT1, but also stabilizes SGLT1 through its kinase-independent mechanism. Taken together, EGFR/SGLT1 maintains intracellular glucose level to prevent cell death in cancer cells through EGFR kinase-independent activity. These results provide the possibility that blockage of the kinase-dependent and -independent activity of EGFR will be a promising therapeutic target for clinical cancer treatment.



1. Wells, A. EGF receptor. Int J Biochem Cell Biol 31, 637-643 (1999).

2. Dancey, J.E. & Freidlin, B. Targeting epidermal growth factor receptor--are we missing the mark? Lancet 362, 62-64 (2003).