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
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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.
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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.
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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.
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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
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Journal ArticleDOI
Imaging proteins in vivo using fluorescence lifetime microscopy
TL;DR: The principles and recent advances in the application of the FLIM technique, instrumentation and molecular probe development are reviewed.
Journal ArticleDOI
Nodal Status and Clinical Outcomes in a Large Cohort of Patients With Triple-Negative Breast Cancer
Leonel Hernandez-Aya,Mariana Chavez-MacGregor,Xiudong Lei,Xiudong Lei,Funda Meric-Bernstam,Thomas A. Buchholz,Limin Hsu,Limin Hsu,Aysegul Sahin,Kim Anh Do,Vicente Valero,Gabriel N. Hortobagyi,Gabriel N. Hortobagyi,Ana M. Gonzalez-Angulo,Ana M. Gonzalez-Angulo +14 more
TL;DR: In patients with TNBC, once there is evidence of lymph node metastasis, the prognosis may not be affected by the number of positive lymph nodes.
Journal ArticleDOI
Site-Directed Perturbation of Protein Kinase C- Integrin Interaction Blocks Carcinoma Cell Chemotaxis
Maddy Parsons,Melanie Keppler,Adam D. Kline,Anthea J. Messent,Martin J. Humphries,R Gilchrist,Ian R. Hart,Corinne Quittau-Prevostel,William E. Hughes,Peter J. Parker,Tony Ng +10 more
TL;DR: It is reported that the phorbol ester-induced cell polarization and directional motility in breast carcinoma cells is determined by a 12-amino-acid motif within the PKCα V3 hinge domain, which outlines a new concept as to how carcinoma cell chemotaxis is enhanced and provides a conceptual basis for interfering with tumor cell dissemination.
Journal ArticleDOI
A common cofilin activity cycle in invasive tumor cells and inflammatory cells.
TL;DR: An overview of cofilin activation in both tumor cells and inflammatory cells is given, and it is proposed that all of the data can be explained by a single activity-cycle model.
Journal ArticleDOI
Regulation of protein tyrosine phosphatase 1B by sumoylation
Shrikrishna Dadke,Shrikrishna Dadke,Sophie Cotteret,Shu-Chin Yip,Zahara M. Jaffer,Fawaz G. Haj,Fawaz G. Haj,Alexey V. Ivanov,Frank J. Rauscher,Ke Shuai,Tony Ng,Benjamin G. Neel,Jonathan Chernoff +12 more
TL;DR: The results suggest that sumoylation, which has been implicated primarily in processes in the nucleus and nuclear pore, also modulates a key enzyme–substrate signalling complex that regulates metabolism and cell proliferation.