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SHR Neuro Krebs Kardio Lipid

Trapp, EK; Majunke, L; Zill, B; Sommer, H; Andergassen, U; Koch, J; Harbeck, N; Mahner, S; Friedl, TWP; Janni, W; Rack, B; Alunni-Fabbroni, M.
LKB1 pro-oncogenic activity triggers cell survival in circulating tumor cells.
Mol Oncol. 2017; 11(11):1508-1526 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Trapp Elisabeth Katharina

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Number of Figures: 9
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During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the epithelial-to-mesenchymal transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress. The aim of this study was to assess LKB1 expression in epithelial-negative CTCs isolated from patients with metastatic breast cancer and to characterize its possible association with EMT and stemness features. Transcriptome analysis of EpCAM-negative CTCs indicated that over 25% of patients showed enhanced LKB1 levels, while almost 20% of patients showed enhanced levels of an EMT transcription factor known as ZEB1. Transcriptome and immunofluorescence analyses showed that patients with enhanced LKB1 were correspondingly ZEB1 negative, suggesting complementary activity for the two proteins. Only ZEB1 was significantly associated with cancer stem cell (CSC) markers. Neither LKB1 nor ZEB1 upregulation showed a correlation with clinical outcome, while enhanced levels of stemness-associated CD44 correlated with a lower progression-free and overall survival. Ex vivo models showed that MDA-MB-231, a mesenchymal tumor cell line, grew in suspension only if LKB1 was upregulated, but the MCF-7 epithelial cell line lost its ability to generate spheroids and colonies when LKB1 was inhibited, supporting the idea that LKB1 might be necessary for CTCs to overcome the absence of the extracellular matrix during the early phases of intravasation. If these preliminary results are confirmed, LKB1 will become a novel therapeutic target for eradicating metastasis-initiating CTCs from patients with primary breast cancer. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Aged -
Breast - metabolism
Breast - pathology
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line, Tumor -
Cell Survival -
Epithelial-Mesenchymal Transition -
Female -
Gene Expression Regulation, Neoplastic -
Humans -
Middle Aged -
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - pathology
Neoplastic Cells, Circulating - metabolism
Neoplastic Cells, Circulating - pathology
Pilot Projects -
Protein-Serine-Threonine Kinases - analysis
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Stress, Physiological -
Transcriptome -

Find related publications in this database (Keywords)
circulating tumor cell
epithelial-to-mesenchymal transition
metabolic stress
metastatic breast cancer
tumor suppressor liver kinase B1
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