Reorganization of ErbB family and cell survival signaling after knock-down of ErbB2 in colon cancer cells

Yi Peter Hu, Srinivas Venkateswarlu, Natalia Sergina, Gillian Howell, Patricia St. Clair, Lisa E. Humphrey, Wenhui Li, Jennie Hauser, Elizabeth Zborowska, James K.V. Willson, Michael G. Brattain

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20 Scopus citations

Abstract

The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody (ScFv5R) against ErbB2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells. The antibody traps ErbB2 in the endoplasmic reticulum, thereby down-regulating cell surface ErbB2. The transfected cells showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3. This resulted in greater sensitivity to apoptosis induced by growth deprivation and delayed tumorigenicity in vivo. Furthermore, decreased heterodimerization of ErbB2 and ErbB3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor (EGFR) and ErbB3 increased, whereas ErbB3 activation remained almost the same. Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells.

Original languageEnglish (US)
Pages (from-to)27383-27392
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number29
DOIs
Publication statusPublished - Jul 22 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hu, Y. P., Venkateswarlu, S., Sergina, N., Howell, G., St. Clair, P., Humphrey, L. E., ... Brattain, M. G. (2005). Reorganization of ErbB family and cell survival signaling after knock-down of ErbB2 in colon cancer cells. Journal of Biological Chemistry, 280(29), 27383-27392. https://doi.org/10.1074/jbc.M414238200