Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor Thr
Cell Line, Tumor
Cell Proliferation
/ physiology
Cell Transformation, Neoplastic
/ metabolism
Cytostatic Agents
/ metabolism
Dimerization
Extracellular Signal-Regulated MAP Kinases
Humans
Phosphorylation
/ physiology
Proto-Oncogene Proteins c-akt
/ metabolism
Receptor Protein-Tyrosine Kinases
/ metabolism
Receptor, ErbB-2
/ immunology
Signal Transduction
/ physiology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 10 2020
09 10 2020
Historique:
received:
05
03
2020
accepted:
16
09
2020
entrez:
10
10
2020
pubmed:
11
10
2020
medline:
13
1
2021
Statut:
epublish
Résumé
ERBB2 is a ligand-less tyrosine kinase receptor expressed at very low levels in normal tissues; when overexpressed, it is involved in malignant transformation and tumorigenesis in several carcinomas. In cancer cells, ERBB2 represents the preferred partner of other members of the ERBB receptor family, leading to stronger oncogenic signals, by promoting both ERK and AKT activation. The identification of the specific signaling downstream of ERBB2 has been impaired by the lack of a ligand and of an efficient way to selectively activate the receptor. In this paper, we found that antibodies (Abs) targeting different epitopes on the ERBB2 extracellular domain foster the activation of ERBB2 homodimers, and surprisingly induce a unique cytostatic signaling cascade promoting an ERK-dependent ERBB2 Thr
Identifiants
pubmed: 33037285
doi: 10.1038/s41598-020-73835-1
pii: 10.1038/s41598-020-73835-1
pmc: PMC7547737
doi:
Substances chimiques
Cytostatic Agents
0
ERBB2 protein, human
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16906Commentaires et corrections
Type : ErratumIn
Références
Press, M. F., Cordon-Cardo, C. & Slamon, D. J. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 5, 953–962 (1990).
pubmed: 1973830
pmcid: 1973830
Segatto, O., Lonardo, F., Pierce, J. H., Bottaro, D. P. & Di Fiore, P. P. The role of autophosphorylation in modulation of erbB-2 transforming function. New Biol. 2, 187–195 (1990).
pubmed: 1982072
pmcid: 1982072
Hudziak, R. M., Schlessinger, J. & Ullrich, A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc. Natl. Acad. Sci. U.S.A. 84, 7159–7163 (1987).
pubmed: 2890160
pmcid: 2890160
Mayer, I. A. Treatment of HER2-positive metastatic breast cancer following initial progression. Clin. Breast Cancer 9(Suppl 2), S50–S57 (2009).
pubmed: 19596643
pmcid: 19596643
Arteaga, C. L. & Engelman, J. A. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25, 282–303 (2014).
pubmed: 24651011
pmcid: 24651011
Jorissen, R. N. et al. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp. Cell Res. 284, 31–53 (2003).
pubmed: 12648464
pmcid: 12648464
Olayioye, M. A., Neve, R. M., Lane, H. A. & Hynes, N. E. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 19, 3159–3167 (2000).
pubmed: 10880430
pmcid: 10880430
Yarden, Y. & Sliwkowski, M. X. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell. Biol. 2, 127–137 (2001).
pubmed: 11252954
pmcid: 11252954
Citri, A. & Yarden, Y. EGF-ERBB signalling: towards the systems level. Nat. Rev. Mol. Cell. Biol. 7, 505–516 (2006).
pubmed: 16829981
pmcid: 16829981
Tzahar, E. et al. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol. Cell. Biol. 16, 5276–5287 (1996).
pubmed: 8816440
pmcid: 8816440
Klapper, L. N. et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc. Natl. Acad. Sci. U.S.A. 96, 4995–5000 (1999).
pubmed: 10220407
pmcid: 10220407
Graus-Porta, D., Beerli, R. R., Daly, J. M. & Hynes, N. E. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 16, 1647–1655 (1997).
pubmed: 9130710
pmcid: 9130710
Cho, H. S. et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421, 756–760 (2003).
pubmed: 12610629
pmcid: 12610629
Garrett, T. P. et al. The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol. Cell 11, 495–505 (2003).
pubmed: 12620236
pmcid: 12620236
Karunagaran, D. et al. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. EMBO J. 15, 254–264 (1996).
pubmed: 8617201
pmcid: 8617201
Harari, D. & Yarden, Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene 19, 6102–6114 (2000).
pubmed: 11156523
pmcid: 11156523
Holbro, T., Civenni, G. & Hynes, N. E. The ErbB receptors and their role in cancer progression. Exp. Cell Res. 284, 99–110 (2003).
pubmed: 12648469
pmcid: 12648469
Nahta, R. & Esteva, F. J. Herceptin: mechanisms of action and resistance. Cancer Lett. 232, 123–138 (2006).
pubmed: 16458110
pmcid: 16458110
Mosesson, Y. & Yarden, Y. Oncogenic growth factor receptors: implications for signal transduction therapy. Semin. Cancer Biol. 14, 262–270 (2004).
pubmed: 15219619
pmcid: 15219619
Baselga, J., Albanell, J., Molina, M. A. & Arribas, J. Mechanism of action of trastuzumab and scientific update. Semin. Oncol. 28, 4–11 (2001).
pubmed: 11706390
pmcid: 11706390
Yakes, F. M. et al. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res. 62, 4132–4141 (2002).
pubmed: 12124352
pmcid: 12124352
Nicholson, K. M. & Anderson, N. G. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 14, 381–395 (2002).
pubmed: 11882383
pmcid: 11882383
Liu, P., Cheng, H., Roberts, T. M. & Zhao, J. J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat. Rev. Drug Discov. 8, 627–644 (2009).
pubmed: 19644473
pmcid: 19644473
Seshacharyulu, P., Pandey, P., Datta, K. & Batra, S. K. Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer. Cancer Lett. 335, 9–18 (2013).
pubmed: 23454242
pmcid: 23454242
Choudhury, A. et al. Small interfering RNA (siRNA) inhibits the expression of the Her2/neu gene, upregulates HLA class I and induces apoptosis of Her2/neu positive tumor cell lines. Int. J. Cancer 108, 71–77 (2004).
pubmed: 14618618
pmcid: 14618618
Faltus, T. et al. Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells. Neoplasia 6, 786–795 (2004).
pubmed: 15720805
pmcid: 15720805
Franklin, M. C. et al. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 5, 317–328 (2004).
pubmed: 15093539
pmcid: 15093539
Carter, P., Fendly, B. M., Lewis, G. D. & Sliwkowski, M. X. Development of herceptin. Breast Dis. 11, 103–111 (2000).
pubmed: 15687596
pmcid: 15687596
Fisher, R. D. et al. Structure of the complex between HER2 and an antibody paratope formed by side chains from tryptophan and serine. J. Mol. Biol. 402, 217–229 (2010).
pubmed: 20654626
pmcid: 20654626
Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell 103, 211–225 (2000).
pubmed: 11057895
pmcid: 11057895
Lehr, S. et al. Identification of major ERK-related phosphorylation sites in Gab1. Biochemistry 43, 12133–12140 (2004).
pubmed: 15379552
pmcid: 15379552
Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P. & Pandolfi, P. P. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 121, 179–193 (2005).
pubmed: 15851026
pmcid: 15851026
Zmajkovicova, K. et al. MEK1 is required for PTEN membrane recruitment, AKT regulation, and the maintenance of peripheral tolerance. Mol. Cell 50, 43–55 (2013).
pubmed: 23453810
pmcid: 23453810
Shah, O. J., Wang, Z. & Hunter, T. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr. Biol. 14, 1650–1656 (2004).
pubmed: 15380067
pmcid: 15380067
Ma, L. et al. Identification of S664 TSC2 phosphorylation as a marker for extracellular signal-regulated kinase mediated mTOR activation in tuberous sclerosis and human cancer. Cancer Res. 67, 7106–7112 (2007).
pubmed: 17671177
pmcid: 17671177
Liao, Y. & Hung, M. C. Physiological regulation of Akt activity and stability. Am. J. Transl. Res. 2, 19–42 (2010).
pubmed: 20182580
pmcid: 20182580
Xiao, L. et al. Protein phosphatase-1 regulates Akt1 signal transduction pathway to control gene expression, cell survival and differentiation. Cell Death Differ. 17, 1448–1462 (2010).
pubmed: 20186153
pmcid: 20186153
Lu, K. P., Finn, G., Lee, T. H. & Nicholson, L. K. Prolyl cis-trans isomerization as a molecular timer. Nat. Chem. Biol. 3, 619–629 (2007).
pubmed: 17876319
pmcid: 17876319
Lin, Z. L., Wu, H. J., Chen, J. A., Lin, K. C. & Hsu, J. H. Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells. Cell. Biochem. Funct. 33, 566–574 (2015).
Obata, T. et al. Peptide and protein library screening defines optimal substrate motifs for AKT/PKB. J. Biol. Chem. 275, 36108–36115 (2000).
pubmed: 10945990
pmcid: 10945990
Sengupta, P. et al. Probing protein heterogeneity in the plasma membrane using PALM and pair correlation analysis. Nat. Methods 8, 969–975 (2011).
pubmed: 21926998
pmcid: 21926998
Pearson, R. B. & Kemp, B. E. Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods Enzymol. 200, 62–81 (1991).
pubmed: 1956339
pmcid: 1956339
Kawasaki, Y. et al. Feedback control of ErbB2 via ERK-mediated phosphorylation of a conserved threonine in the juxtamembrane domain. Sci. Rep. 6, 31502 (2016).
pubmed: 27531070
pmcid: 27531070
Li, X., Huang, Y., Jiang, J. & Frank, S. J. ERK-dependent threonine phosphorylation of EGF receptor modulates receptor downregulation and signaling. Cell Signal. 20, 2145–2155 (2008).
pubmed: 18762250
pmcid: 18762250
RedBrewer, M. et al. The juxtamembrane region of the EGF receptor functions as an activation domain. Mol. Cell 34, 641–651 (2009).
Hazan, R. et al. Identification of autophosphorylation sites of HER2/neu. Cell Growth Differ. 1, 3–7 (1990).
pubmed: 1706616
pmcid: 1706616
Weiwad, M., Kullertz, G., Schutkowski, M. & Fischer, G. Evidence that the substrate backbone conformation is critical to phosphorylation by p42 MAP kinase. FEBS Lett. 478, 39–42 (2000).
pubmed: 10922466
pmcid: 10922466
Bessman, N. J., Freed, D. M. & Lemmon, M. A. Putting together structures of epidermal growth factor receptors. Curr. Opin. Struct. Biol. 29, 95–101 (2014).
pubmed: 25460273
pmcid: 25460273
Fuentes, G., Scaltriti, M., Baselga, J. & Verma, C. S. Synergy between trastuzumab and pertuzumab for human epidermal growth factor 2 (Her2) from colocalization: an in silico based mechanism. Breast Cancer Res 13, R54 (2011).
pubmed: 21600050
pmcid: 21600050
Franco-Gonzalez, J. F., Ramos, J., Cruz, V. L. & Martinez-Salazar, J. Exploring the dynamics and interaction of a full ErbB2 receptor and Trastuzumab-Fab antibody in a lipid bilayer model using Martini coarse-grained force field. J. Comput. Aid. Mol. Des. 28, 1093–1107 (2014).
Wang, P. & Heitman, J. The cyclophilins. Genome Biol. 6, 226 (2005).
pubmed: 15998457
pmcid: 15998457
Wulf, G., Ryo, A., Liou, Y. C. & Lu, K. P. The prolyl isomerase Pin1 in breast development and cancer. Breast Cancer Res. 5, 76–82 (2003).
pubmed: 12631385
pmcid: 12631385
Stancovski, I. et al. Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth. Proc. Natl. Acad. Sci. U.S.A. 88, 8691–8695 (1991).
pubmed: 1717984
pmcid: 1717984
Lam, P. B. et al. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability. Mol. Cancer 7, 91 (2008).
pubmed: 19077306
pmcid: 19077306
Obchoei, S. et al. Cyclophilin A: potential functions and therapeutic target for human cancer. Med Sci Monit 15, RA221–RA232 (2009).
pubmed: 19865066
pmcid: 19865066
Lee, J. & Kim, S. S. Current implications of cyclophilins in human cancers. J. Exp. Clin. Cancer Res. 29, 97 (2010).
pubmed: 20637127
pmcid: 20637127
Hamel, S. et al. Both t-Darpp and DARPP-32 can cause resistance to trastuzumab in breast cancer cells and are frequently expressed in primary breast cancers. Breast Cancer Res. Treat. 120, 47–57 (2010).
pubmed: 19301121
pmcid: 19301121
Sato, K. et al. Inverse correlation between Thr-669 and constitutive tyrosine phosphorylation in the asymmetric epidermal growth factor receptor dimer conformation. Cancer Sci. 104, 1315–1322 (2013).
pubmed: 23822636
pmcid: 23822636
Hsu, T., McRackan, D., Vincent, T. S. & Gert de Couet, H. Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis. Nat. Cell Biol. 3, 538–543 (2001).
pubmed: 11389437
pmcid: 11389437
Huang, B. X. & Kim, H. Y. Effective identification of Akt interacting proteins by two-step chemical crosslinking, co-immunoprecipitation and mass spectrometry. PLoS ONE 8, e61430 (2013).
pubmed: 23613850
pmcid: 23613850
Shevchenko, A., Wilm, M., Vorm, O. & Mann, M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68, 850–858 (1996).
pubmed: 8779443
pmcid: 8779443
Magagnotti, C. et al. Identification of nephropathy predictors in urine from children with a recent diagnosis of type 1 diabetes. J. Proteomics 193, 205–216 (2019).
pubmed: 30366120
pmcid: 30366120
Thingholm, T. E., Jorgensen, T. J., Jensen, O. N. & Larsen, M. R. Highly selective enrichment of phosphorylated peptides using titanium dioxide. Nat. Protoc. 1, 1929–1935 (2006).
pubmed: 17487178
pmcid: 17487178
Niada, S., Giannasi, C., Gualerzi, A., Banfi, G. & Brini, A. T. Differential proteomic analysis predicts appropriate applications for the secretome of adipose-derived mesenchymal stem/stromal cells and dermal fibroblasts. Stem Cells Int. 2018, 7309031 (2018).
pubmed: 30158987
pmcid: 30158987
Barber, D. S., Stevens, S. & LoPachin, R. M. Proteomic analysis of rat striatal synaptosomes during acrylamide intoxication at a low dose rate. Toxicol. Sci. 100, 156–167 (2007).
pubmed: 17698512
pmcid: 17698512