Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways
Xinyan Wu,Muhammad Saddiq Zahari,Binyun Ma,Ren Liu,Santosh Renuse,Nandini A. Sahasrabuddhe,Lily Chen,Raghothama Chaerkady,Min-Sik Kim,Jun Zhong,Christine A. Jelinek,Mustafa A. Barbhuiya,Pamela Leal-Rojas,Pamela Leal-Rojas,Yi Yang,Manoj Kumar Kashyap,Arivusudar Marimuthu,Min Ling,Mary Jo Fackler,Vanessa F. Merino,Zhen Zhang,Cynthia A. Zahnow,Edward Gabrielson,Vered Stearns,Juan Carlos Roa,Saraswati Sukumar,Parkash S. Gill,Akhilesh Pandey +27 more
TLDR
The phosphotyrosine proteome analysis provided new insights into the heterogeneity in the activation status of tyrosine kinase pathways in TNBCs and presented an effective means of identifying important novel biomarkers and targets for therapy such as AXL in T NBC.Abstract:
Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers are triple negative breast cancer (TNBC) and are often highly aggressive when compared to other subtypes of breast cancers. To better characterize the biology that underlies the TNBC phenotype, we profiled the phosphotyrosine proteome of a panel of twenty-six TNBC cell lines using quantitative high resolution Fourier transform mass spectrometry. A heterogeneous pattern of tyrosine kinase activation was observed based on 1,789 tyrosine-phosphorylated peptides identified from 969 proteins. One of the tyrosine kinases, AXL, was found to be activated in a majority of aggressive TNBC cell lines and was accompanied by a higher level of AXL expression. High levels of AXL expression are correlated with a significant decrease in patient survival. Treatment of cells bearing activated AXL with a humanized AXL antibody inhibited cell proliferation and migration in vitro, and tumor growth in mice. Overall, our global phosphoproteomic analysis provided new insights into the heterogeneity in the activation status of tyrosine kinase pathways in TNBCs. Our approach presents an effective means of identifying important novel biomarkers and targets for therapy such as AXL in TNBC.read more
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The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression
Marie-Anne Goyette,Stéphanie Duhamel,Léo Aubert,Ariane Pelletier,Paul Savage,Marie-Pier Thibault,Radia M. Johnson,Peter Carmeliet,Mark Basik,Louis Gaboury,William J. Muller,Morag Park,Philippe P. Roux,Jean-Philippe Gratton,Jean-François Côté +14 more
TL;DR: Using murine models of HER2+ breast cancer, Axl, but not its ligand Gas6, was found to be essential for metastasis, and pharmacological inhibition of AXL specifically decreased the metastatic burden of mice developing HER2-positive breast cancer.
Journal ArticleDOI
Ultrasensitive determination of receptor tyrosine kinase with a label-free electrochemical immunosensor using graphene quantum dots-modified screen-printed electrodes
Fariba Mollarasouli,Verónica Serafín,Susana Campuzano,Paloma Yáñez-Sedeño,José M. Pingarrón,José M. Pingarrón,Karim Asadpour-Zeynali +6 more
TL;DR: The developed immunosensor was successfully applied to the determination of the endogenous content of AXL in serum of HF patients without any matrix effect observed after just a sample dilution.
Journal ArticleDOI
Oncogenic Kinase-Induced PKM2 Tyrosine 105 Phosphorylation Converts Nononcogenic PKM2 to a Tumor Promoter and Induces Cancer Stem-like Cells.
Zhifen Zhou,Zhifen Zhou,Min Li,Lin Zhang,Hong Zhao,Ozgur Sahin,Jing Chen,Jean J. Zhao,Zhou Songyang,Zhou Songyang,Dihua Yu,Dihua Yu +11 more
TL;DR: Phosphorylation of PKM2-Y105 by activated kinases exerts oncogenic functions in part via activation of YAP downstream signaling to increase cancer stem-like cell properties.
Journal ArticleDOI
Protein biomarkers for subtyping breast cancer and implications for future research.
TL;DR: This review provides a summary of immunohistochemistry, reverse phase protein array, mass spectrometry, and integrative studies that are revealing differences in biological functions within and between breast cancer subtypes and discusses rigor and reproducibility for proteomic-based biomarker discovery.
Journal ArticleDOI
Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-kB Activity in Triple-Negative Breast Cancer Cells.
TL;DR: It is reported that Pyruvate kinase muscle is a potential therapeutic target in triple-negative breast cancer (TNBC) cells and found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells.
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