EGFR protects cancer cells from starvation via a kinase-independent mechanism

The researchers found that the EGFR enables human cancer cells to maintain adequate intracellular glucose levels by stabilizing the sodium/glucose transporter 1 (SGLT1) via a kinase-independent mechanism. Glucose is a major energy substrate for all cells, and without appropriate amounts, cells essentially starve to death through a process called autophagic cell death. Cancer cells are very active metabolically and consume more glucose than normal tissues; moreover, the EGFR overexpression and the associated enhanced stability of SGLT1 allow tumor cells to survive under conditions that would be less than optimal, even for normal cells.

“Our results suggest that EGFR, independent of its kinase activity, maintains the basal intracellular glucose level and thereby prevents cancer cells from succumbing to autophagic death. It is possible that this function of the EGFR may even increase the survival capacity of cancer cells in the presence of chemotherapeutic agents,” offers study author Dr. Mien-Chie Hung. The researchers suggest that inhibition of both EGFR-mediated SGLT1 stabilization and EGFR kinase activity may be necessary for eradication of epithelial tumors.

The researchers include Zhang Weihua, Rachel Tsan, Wei-Chien Huang, Qiuyu Wu, Chao-Hua Chiu, Isaiah J. Fidler, and Mien-Chie Hung of The University of Texas M.D. Anderson Cancer Center in Houston, Texas.

This work was supported in part by SPORE in Prostate Cancer CA-90270, SPORE in Breast Cancer CA-116199 and Cancer Center Support Core grant CA-16672, the National Cancer Institute, National Institutes of Health, and an Odyssey Fellowship Award from The University of Texas M.D. Anderson Cancer Center.

Weihua et al.: “Survival of Cancer Cells Is Maintained by EGFR Independent of its Kinase Activity.” Publishing in Cancer Cell 13, 385–393, May 2008. DOI 10.1016/j.ccr.2008.03.015 www.cancercell.org