EGF-induced Grb7 recruits and promotes Ras activity essential for the tumorigenicity of Sk-Br3 breast cancer cells.

The Journal of Biological Chemistry
Pei-Yu ChuTang-Long Shen

Abstract

Co-amplification and co-overexpression of ErbB2 and Grb7 are frequently found in various cancers, including breast cancer. Biochemical and functional correlations of the two molecules have identified Grb7 to be a pivotal mediator downstream of ErbB2-mediated oncogenesis. However, it remains largely unknown how Grb7 is involve in the ErbB2-mediated tumorigenesis. In this study, we show that Grb7-mediated cell proliferation and growth are essential for the tumorigenesis that occurs in ErbB2-Grb7-overexpressing breast cancer cells. Intrinsically, EGF-induced de novo Grb7 tyrosine phosphorylation/activation recruits and activates Ras-GTPases and subsequently promotes the phosphorylation of ERK1/2, thereby stimulating tumor growth. Furthermore, we also found the anti-tumor effect could be synergized by co-treatment with Herceptin plus Grb7 knockdown in Sk-Br3 breast cancer cells. Our findings illustrate an underlying mechanism by which Grb7 promotes tumorigenesis through the formation of a novel EGFR-Grb7-Ras signaling complex, thereby highlighting the potential strategy of targeting Grb7 as an anti-breast cancer therapy.

References

Oct 30, 1998·Cellular Signalling·R J Daly
Aug 14, 1999·The Journal of Biological Chemistry·D C Han, J L Guan
May 8, 2000·Journal of Cellular Physiology·S TanakaJ R Wands
Mar 30, 2001·The Journal of Biological Chemistry·R J LyonsR J Daly
May 22, 2002·The Journal of Biological Chemistry·Tang-Long ShenJun-Lin Guan
Sep 12, 2002·The Journal of Biological Chemistry·Dong Cho HanJun-Lin Guan
Feb 10, 2004·Frontiers in Bioscience : a Journal and Virtual Library·Tang-Long Shen, Jun-Lin Guan
May 15, 2004·Molecular and Cellular Biology·Pablo Rodriguez-VicianaFrank McCormick
Oct 26, 2005·Molecular Cell·Rafael S DepetrisStevan R Hubbard
Nov 18, 2005·Methods : a Companion to Methods in Enzymology·Ariel F CastroLawrence A Quilliam
Apr 6, 2006·Journal of the National Cancer Institute·Shinji TanakaShigeki Arii
Nov 23, 2006·British Journal of Cancer·P R BenusiglioB A J Ponder
Jul 20, 2007·Molecular Cancer Research : MCR·Shinji ItohYoshihiko Maehara
Oct 6, 2007·Carcinogenesis·Tao Bai, Shiuh-Wen Luoh
Mar 1, 2008·Current Genomics·E Lucas-FernándezA Villalobo
Aug 4, 2009·Nature Structural & Molecular Biology·Rafael S DepetrisStevan R Hubbard
Sep 1, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Y NadlerY Kluger
Oct 29, 2009·Carcinogenesis·Pamela K Kreeger, Douglas A Lauffenburger

❮ Previous
Next ❯

Citations

Oct 19, 2011·Breast Cancer Research and Treatment·Orsi GiriczParaic A Kenny
Aug 27, 2013·Breast Cancer Research : BCR·Siddhartha DebStephen B Fox
Jan 28, 2014·Breast Cancer Research and Treatment·Reece C C LimJacqueline A Wilce
Sep 4, 2014·Medical Oncology·Amal Said DarweeshSamar Kamal Kassim
Sep 12, 2015·Journal of Medicinal Chemistry·Gabrielle M WatsonJacqueline A Wilce
Oct 10, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Yen-Wen WangTang-Long Shen
Jan 21, 2012·Biochemical Society Transactions·Edita AksamitieneBoris N Kholodenko
Oct 14, 2011·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Jianping ZhangSusan J Braunhut
Aug 11, 2015·Analytical Cellular Pathology (Amsterdam)·Kallirroi VoudouriDragana Nikitovic
Feb 23, 2020·International Journal of Molecular Sciences·Gabrielle M Watson, Jacqueline A Wilce
Apr 25, 2019·International Journal of Molecular Medicine·Yiyin TangQian Zhang
Oct 12, 2017·Frontiers in Molecular Biosciences·Gabrielle M WatsonJacqueline A Wilce
Nov 15, 2013·American Journal of Physiology. Renal Physiology·Xiaofan WeiHongquan Zhang
Feb 12, 2013·Chemical Society Reviews·Dziyana KraskouskayaPatrick T Gunning
Oct 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jianrong SangJacqueline A Wilce
May 4, 2020·Archives of Biochemistry and Biophysics·Irene García-PalmeroAntonio Villalobo
Jan 14, 2021·Cancer Research·Ana P KutschatSteven A Johnsen
Oct 31, 2017·Journal of Medicinal Chemistry·Gabrielle M WatsonJacqueline A Wilce

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.