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

Research output: Contribution to journalArticle

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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
StatePublished - Jul 22 2005

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Cell signaling
Epidermal Growth Factor Receptor
Colonic Neoplasms
Cell Survival
Chemical activation
Cells
Single-Chain Antibodies
Phosphorylation
Endoplasmic Reticulum
Tyrosine
Apoptosis
Antibodies
Transfection
Colon
Carcinoma
Phenotype
Growth

ASJC Scopus subject areas

  • Biochemistry

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

Reorganization of ErbB family and cell survival signaling after knock-down of ErbB2 in colon cancer cells. / Hu, Yi Peter; Venkateswarlu, Srinivas; Sergina, Natalia; Howell, Gillian; St. Clair, Patricia; Humphrey, Lisa E.; Li, Wenhui; Hauser, Jennie; Zborowska, Elizabeth; Willson, James K V; Brattain, Michael G.

In: Journal of Biological Chemistry, Vol. 280, No. 29, 22.07.2005, p. 27383-27392.

Research output: Contribution to journalArticle

Hu, YP, Venkateswarlu, S, Sergina, N, Howell, G, St. Clair, P, Humphrey, LE, Li, W, Hauser, J, Zborowska, E, Willson, JKV & Brattain, MG 2005, 'Reorganization of ErbB family and cell survival signaling after knock-down of ErbB2 in colon cancer cells', Journal of Biological Chemistry, vol. 280, no. 29, pp. 27383-27392. https://doi.org/10.1074/jbc.M414238200
Hu, Yi Peter ; Venkateswarlu, Srinivas ; Sergina, Natalia ; Howell, Gillian ; St. Clair, Patricia ; Humphrey, Lisa E. ; Li, Wenhui ; Hauser, Jennie ; Zborowska, Elizabeth ; Willson, James K V ; Brattain, Michael G. / Reorganization of ErbB family and cell survival signaling after knock-down of ErbB2 in colon cancer cells. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 29. pp. 27383-27392.
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