Imaging tumour heterogeneity of the consequences of a PKCα-substrate interaction in breast cancer patients.
Gregory Weitsman,Katherine Lawler,Muireann Kelleher,James E. Barrett,Paul R. Barber,E Shamil,Frederic Festy,Gargi Patel,Gilbert O. Fruhwirth,Lufei Huang,Iain D. C. Tullis,Natalie Woodman,Enyinnaya Ofo,Simon Ameer-Beg,Sheeba Irshad,John S. Condeelis,Cheryl Gillett,Paul Ellis,Borivoj Vojnovic,Borivoj Vojnovic,Anthony C. C. Coolen,Tony Ng,Tony Ng +22 more
TLDR
It is demonstrated that tissue imaging-derived parameters that pertain to or are a consequence of the PKC-ezrin interaction can be used for breast cancer prognostication, with inter-cohort reproducibility.Abstract:
Breast cancer heterogeneity demands that prognostic models must be biologically driven and recent clinical evidence indicates that future prognostic signatures need evaluation in the context of early compared with late metastatic risk prediction. In pre-clinical studies, we and others have shown that various protein–protein interactions, pertaining to the actin microfilament-associated proteins, ezrin and cofilin, mediate breast cancer cell migration, a prerequisite for cancer metastasis. Moreover, as a direct substrate for protein kinase Cα, ezrin has been shown to be a determinant of cancer metastasis for a variety of tumour types, besides breast cancer; and has been described as a pivotal regulator of metastasis by linking the plasma membrane to the actin cytoskeleton. In the present article, we demonstrate that our tissue imaging-derived parameters that pertain to or are a consequence of the PKC–ezrin interaction can be used for breast cancer prognostication, with inter-cohort reproducibility. The application of fluorescence lifetime imaging microscopy (FLIM) in formalin-fixed paraffin-embedded patient samples to probe protein proximity within the typicallyread more
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Macrophage-dependent tumor cell transendothelial migration is mediated by Notch1/Mena INV-initiated invadopodium formation
Jeanine Pignatelli,Jose Javier Bravo-Cordero,Minna Roh-Johnson,Minna Roh-Johnson,Saumil J. Gandhi,Yarong Wang,Xiaoming Chen,Robert J. Eddy,Alice Xue,Robert H. Singer,Louis Hodgson,Maja H. Oktay,John S. Condeelis +12 more
TL;DR: A novel role for Notch1 signaling in the regulation of MenaINV expression and transendothelial migration is indicated and mechanistic information essential to the use of therapeutic inhibitors of metastasis is provided.
Journal ArticleDOI
Signatures of breast cancer metastasis at a glance
TL;DR: Prognostic assays based on proliferation based on Oncotype DX, MammaPrint DX and TMEM score combined with a prognostic derived from a signature of dissemination could provide a complementary and more personalized prognostic information for breast cancer patients.
Journal ArticleDOI
Quantification of HER family receptors in breast cancer
TL;DR: The current available methodologies to measure HER family receptors are presented and the clinical implications of target quantification are discussed.
Journal ArticleDOI
HER2-HER3 dimer quantification by FLIM-FRET predicts breast cancer metastatic relapse independently of HER2 IHC status
Gregory Weitsman,Paul R. Barber,Lan K. Nguyen,Katherine Lawler,Gargi Patel,Natalie Woodman,Muireann Kelleher,Sarah E Pinder,Mark Rowley,Paul Ellis,Anand D. Purushotham,A C C Coolen,Boris N. Kholodenko,Borivoj Vojnovic,Borivoj Vojnovic,Cheryl Gillett,Tony Ng +16 more
TL;DR: Analysis of 131 tissue microarray cores demonstrated that the extent of HER2-HER3 dimer formation as measured by Förster Resonance Energy Transfer determined through FLIM predicts the likelihood of metastatic relapse up to 10 years after surgery, and Interestingly there was no correlation between the level of Her2 protein expressed and Her2- HER3 heterodimer formation.
Journal ArticleDOI
HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial.
Paul R. Barber,Gregory Weitsman,Katherine Lawler,James E. Barrett,Mark Rowley,Manuel Rodriguez-Justo,David E. Fisher,Fangfei Gao,Iain D. C. Tullis,Jinhai Deng,Louise Brown,Richard Kaplan,Daniel Hochhauser,Richard Adams,Tim Maughan,Borivoj Vojnovic,Anthony C. C. Coolen,Tony Ng,Tony Ng +18 more
TL;DR: The combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy and confirm its utility in predicting the outcome of anti-EGFR treatment.
References
More filters
Journal ArticleDOI
Network-based classification of breast cancer metastasis.
TL;DR: A protein‐network‐based approach is applied that identifies markers not as individual genes but as subnetworks extracted from protein interaction databases, which provide novel hypotheses for pathways involved in tumor progression.
Journal ArticleDOI
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009
TL;DR: The 11th St Gallen expert consensus meeting on the primary treatment of early breast cancer in March 2009 maintained an emphasis on targeting adjuvant systemic therapies according to subgroups defined by predictive markers, acknowledging the role of risk factors with the caveat that risk per se is not a target.
Journal ArticleDOI
Protein kinase C alpha activates RAF-1 by direct phosphorylation
Walter Kolch,Gisela Heidecker,Georg Kochs,Richard Hummel,Haleh Vahidi,Harald Mischak,Günter Finkenzeller,Dieter Marmé,Ulf R. Rapp +8 more
TL;DR: The observation that Raf-1 and PKCα cooperate in the transformation of NIH3T3 cells is consistent with such a direct interaction, and the Ser499 phosphorylation site is necessary for this synergism.
Journal ArticleDOI
Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer
Marc Buyse,Sherene Loi,Laura J. van't Veer,Giuseppe Viale,Mauro Delorenzi,Annuska M. Glas,Mahasti Saghatchian d'Assignies,Jonas Bergh,Rosette Lidereau,Paul Ellis,Adrian L. Harris,Jan Bogaerts,Patrick Therasse,Arno Floore,Mohamed Amakrane,Fanny Piette,Emiel J. Th. Rutgers,Christos Sotiriou,Fatima Cardoso,Martine Piccart +19 more
TL;DR: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer and outperformed the clinicopathological risk assessment in predicting all endpoints.
Journal ArticleDOI
Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids.
TL;DR: The proenzyme of a Ca2+-dependent protease-activated protein kinase previously obtained from mammalian tissues showed an ability to phosphorylate five histone fractions and muscle phosphorylase kinase, and appeared to possess multifunctional catalytic activities.