Analysis of Hierarchical Organization in Gene Expression Networks Reveals Underlying Principles of Collective Tumor Cell Dissemination and Metastatic Aggressiveness of Inflammatory Breast Cancer

Frontiers in Oncology
Shubham TripathiMichael W Deem

Abstract

Clusters of circulating tumor cells (CTCs), despite being rare, may account for more than 90% of metastases. Cells in these clusters do not undergo a complete epithelial-to-mesenchymal transition (EMT), but retain some epithelial traits as compared to individually disseminating tumor cells. Determinants of single cell dissemination versus collective dissemination remain elusive. Inflammatory breast cancer (IBC), a highly aggressive breast cancer subtype that chiefly metastasizes via CTC clusters, is a promising model for studying mechanisms of collective tumor cell dissemination. Previous studies, motivated by a theory that suggests physical systems with hierarchical organization tend to be more adaptable, have found that the expression of metastasis-associated genes is more hierarchically organized in cases of successful metastases. Here, we used the cophenetic correlation coefficient (CCC) to quantify the hierarchical organization in the expression of two distinct gene sets, collective dissemination-associated genes and IBC-associated genes, in cancer cell lines and in tumor samples from breast cancer patients. Hypothesizing that a higher CCC for collective dissemination-associated genes and for IBC-associated genes would be ...Continue Reading

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Citations

Jul 1, 2020·F1000Research·Shensi Shen, Jean Clairambault
Jan 28, 2021·Biomolecules·Jordi Badia-RamentolAlexandre Calon
Jan 31, 2021·Cell Division·Julia BonnetValérie Lobjois
Oct 1, 2018·Pharmacology & Therapeutics·Mohit Kumar JollyHerbert Levine

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Datasets Mentioned

BETA
GSE66527

Methods Mentioned

BETA
biopsies

Software Mentioned

GSEA
MATLAB
CellMiner

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