A novel mechanism for integrin-mediated ras activation in breast carcinoma cells: the alpha6beta4 integrin regulates ErbB2 translation and transactivates epidermal growth factor receptor/ErbB2 signaling

Cancer Research
Sang-Oh YoonElizabeth A Lipscomb

Abstract

ErbB2 (HER2, Neu) and Ras play key roles in tumor invasion and metastasis. We identified a novel mechanism by which integrin alpha(6)beta(4) regulates ErbB2 expression, Ras activation, and the invasion of breast carcinoma cells. Here we show that integrin alpha(6)beta(4) regulates Ras activity especially in serum-depleted condition. Down-regulation of beta(4) integrin by beta(4) short hairpin RNA (shRNA) decreased Ras activity and carcinoma invasion whereas reexpression of this integrin restored Ras activity. ErbB2, a binding partner of epidermal growth factor receptor (EGFR), and EGFR modulated Ras activity, and integrin alpha(6)beta(4) regulated phospho-EGFR level without affecting EGFR expression. We also found that integrin alpha(6)beta(4) is involved in ErbB2 expression. Depletion of beta(4) by shRNA reduced ErbB2 protein level without affecting ErbB2 mRNA level and reexpression of beta(4) increased ErbB2 protein level. Reduction of eukaryotic initiation factor 4E, a rate-limiting factor for cap-dependent translation, decreased ErbB2 protein level, and beta(4) shRNA cells exhibited a shift in ErbB2 mRNA to light polysomes compared with control cells. These results show that integrin alpha(6)beta(4) regulates ErbB2 through ...Continue Reading

References

Jul 1, 1995·Breast Cancer Research and Treatment·G J Clark, C J Der
Jan 1, 1995·Methods in Cell Biology·E Davies, S Abe
Mar 16, 2000·Breast Cancer Research and Treatment·L FlanaganJ Welsh
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Apr 27, 2001·Experimental & Molecular Medicine·C D BaeJ B Park
Apr 27, 2001·Seminars in Cancer Biology·A M Mercurio, I Rabinovitz
Sep 7, 2001·Current Opinion in Cell Biology·A M MercurioL M Shaw
Sep 8, 2001·Journal of Mammary Gland Biology and Neoplasia·A M MercurioT Tani
Jun 25, 2002·Nature Cell Biology·Sebastien JauliacAlex Toker
Jan 2, 2003·Nature Reviews. Cancer·Julian Downward
Oct 2, 2003·Current Opinion in Cell Biology·Paolo M ComoglioLivio Trusolino
Nov 6, 2003·Clinical & Experimental Metastasis·Elizabeth A LipscombArthur M Mercurio
Apr 20, 2004·Oncogene·Eric C HollandGeorge Thomas
Apr 20, 2004·Oncogene·Arrigo De Benedetti, Jeremy R Graff
May 27, 2004·The Journal of Biological Chemistry·Jun ChungArthur M Mercurio
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Wenjun Guo, Filippo G Giancotti
Oct 19, 2004·Seminars in Oncology·Yosef YardenDavid Miles
Nov 16, 2004·Cancer Cell·Yan M LiMien-Chie Hung
Nov 16, 2004·Cancer Cell·Sotiris N NikolopoulosFilippo G Giancotti
Dec 22, 2004·The Journal of Cell Biology·Xiuwei YangMartin E Hemler
May 3, 2005·Nature Reviews. Cancer·Nancy E Hynes, Heidi A Lane

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Citations

Feb 9, 2008·Cellular and Molecular Life Sciences : CMLS·M J Wieduwilt, M M Moasser
Jul 3, 2007·Journal of Mammary Gland Biology and Neoplasia·Donald E White, William J Muller
Mar 15, 2011·Medical Oncology·B PetricevicV Bali
Aug 11, 2006·Nature Biotechnology·David L Rimm
Dec 24, 2009·Nature Reviews. Cancer·Jay S Desgrosellier, David A Cheresh
Apr 12, 2012·The Journal of Biological Chemistry·Kristina R KligysJonathan C R Jones
May 15, 2007·Canadian Journal of Microbiology·Wenbin LiuChengchao Shou
Feb 27, 2007·Breast Cancer Research : BCR·Giulia BonRita Falcioni
Apr 24, 2012·ISRN Oncology·Arthur W LambertSam Thiagalingam
Jun 30, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Rachel L Stewart, Kathleen L O'Connor
Apr 24, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Sung-Im DoDuk-Hwan Kim
Oct 17, 2014·In Vitro Cellular & Developmental Biology. Animal·Feng ZhaoQing-Zhang Li
Jan 26, 2007·The International Journal of Biochemistry & Cell Biology·Elad Katz, Charles H Streuli
Oct 26, 2007·The Journal of Investigative Dermatology·Olivia WansburyBeatrice Howard
Feb 1, 2008·Proteomics. Clinical Applications·Metodi Metodiev, Louise Alldridge
Feb 27, 2008·Microscopy Research and Technique·Jun Chung, Tae Hyong Kim
Jun 9, 2020·PloS One·Florian WeinbergNiels de Jonge
Jan 11, 2020·Frontiers in Oncology·Wei MuMargot Zöller
May 11, 2019·Stem Cells International·Heriberto Abraham Valencia-GonzálezAlejandro García-Carrancá
Feb 21, 2009·The Biochemical Journal·Charles H Streuli, Nasreen Akhtar
Nov 5, 2010·Molecular Cancer Research : MCR·Nadejda L KorneevaJun Chung
Jan 28, 2021·Scientific Reports·Vladimir V StrelnikovOlga A Simonova
Aug 28, 2021·Biomolecules·Haoyu YangYang Xiang
Jun 26, 2008·The International Journal of Biochemistry & Cell Biology·Daniela LössnerUte Reuning

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