Systematic Analysis of the Functional Relevance of Nuclear Structure and Mechanics in Breast Cancer Progression.

摘要

The central hypothesis of this proposal is that changes in the expression of nuclear envelope proteins such as lamins or lamin B receptor (LBR) may contribute to the characteristic irregular morphology of cancer cell nuclei and directly modulate cellular functions relevant to cancer progression. Nuclear lamins, particularly lamins A and C, are important determinants of nuclear shape and stiffness.1-3 At the same time, these proteins also interact with various transcription factors, thereby affecting important signaling pathways.1, 4 The purpose of this study is to conduct a systematic analysis of the functional consequences of changes in the expression of lamins (A, B1, B2, and C) and lamin B receptor on nuclear morphology and stiffness, as well as the functional consequences of such changes on cell migration through confined spaces (where more deformable nuclei may facilitate enhanced passage), proliferation, and epithelial-to-mesenchymal transition (EMT). In addition, we proposed to conduct an analysis of samples derived from breast cancer patients and orthotopic mouse models of the disease to assess changes in the expression of nuclear envelope proteins in breast cancer samples.