Molecular factors influencing epithelial-mesenchymal transition in breast cancer

摘要: Epithelial-mesenchymal transition (EMT) is a developmental process defined by loss of epithelial characteristics and acquisition mesenchymal phenotype. EMT or similar processes are also implicated in carcinoma cell invasion the progression breast to metastasis. In model system for mammary carcinogenesis it has previously been shown that signaling from oncogenic receptor tyrosine kinase cerbB2 (HER2), frequently overexpressed cancers, induces EMT. this system, c-erbB2-induced was significantly delayed high cell-density cellcell-dissociation occurred before downregulation adhesion molecule Ecadherin. Loss E-cadherin expression generally viewed as fundamental event This thesis shows ectopic concomitant with did not hinder expressed cells had weaker attachment cytoskeleton, implicating rearrangement cytoskeleton an important mechanism EMT-associated cellcell-dissociation. Expression dominant negative weakened cell-cell but enable at cell-density. These finding indicate consequence rather than cause density-dependent inhibition mediated E-cadherin. The transcription factor nuclear I-C2 (NFI-C2) lost during tumor NFIC2 counteract repressing Forkhead box F1 (FoxF1). FoxF1 invasiveness cancer cells. thesis, Affymetrix microarray used find oppositely regulated targets NFI-C2 FoxF1. extracellular matrix enzyme lysyl oxidase (LOX) found be negatively positively responsible increased caused overexpression. A pathway identified where FoxF1-induced upregulation LOX activated focal kinase, subsequently suppressing Smad2 activity. parallel, overexpression p38 MAPK pathway. findings give new insights into regulation pathways known progression. Based on suppresses EMT, prognostic value mixed cohort patients investigated. powerful marker associated good prognosis cancer.