Imaging tumour heterogeneity of the consequences of a PKCα-substrate interaction in breast cancer patients.

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 typically <10 nm range to address the oncological challenge of tumour heterogeneity, is discussed.

journal_name

Biochem Soc Trans

authors

Weitsman G,Lawler K,Kelleher MT,Barrett JE,Barber PR,Shamil E,Festy F,Patel G,Fruhwirth GO,Huang L,Tullis ID,Woodman N,Ofo E,Ameer-Beg SM,Irshad S,Condeelis J,Gillett CE,Ellis PA,Vojnovic B,Coolen AC,Ng T

doi

10.1042/BST20140165

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

1498-505

issue

6

eissn

0300-5127

issn

1470-8752

pii

BST20140165

journal_volume

42

pub_type

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