Mechanistic Insights into Colorectal Cancer Phenomics from Fundamental and Organotypic Model Studies

Frederick C Campbell, Maurice Bernard Loughrey, Jane McClements, Ravi Kiran Deevi, Arman Javadi, Lisa Rainey

Research output: Contribution to journalReview article

3 Citations (Scopus)
273 Downloads (Pure)

Abstract

Colorectal cancer (CRC) diagnosis and prognostic stratification are based on histopathologic assessment of cell or nuclear pleomorphism, aberrant mitotic figures, altered glandular architecture, and other phenomic abnormalities. This complexity is driven by oncogenic perturbation of tightly coordinated spatiotemporal signaling to disrupt multiple scales of tissue organization. This review clarifies molecular and cellular mechanisms underlying common CRC histologic features and helps understand how the CRC genome controls core aspects of tumor aggressiveness. It further explores a spatiotemporal framework for CRC phenomics based on regulation of living cells in fundamental and organotypic model systems. The review also discusses tissue homeostasis, considers distinct classes of oncogenic perturbations, and evolution of cellular or multicellular cancer phenotypes. It further explores the molecular controls of cribriform, micropapillary, and high-grade CRC morphology in organotypic culture models and assesses relevant translational studies. In addition, the review delves into complexities of morphologic plasticity whereby a single molecular signature generates heterogeneous cancer phenotypes, and, conversely, morphologically homogeneous tumors show substantive molecular diversity. Principles outlined may aid mechanistic interpretation of omics data in a setting of cancer pathology, provide insight into CRC consensus molecular subtypes, and better define principles for CRC prognostic stratification.

Original languageEnglish
Pages (from-to)1936-1948
JournalThe American journal of pathology
Volume188
Issue number9
Early online date18 Jul 2018
DOIs
Publication statusPublished - 01 Sep 2018

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