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

The American Journal of Pathology
Frederick C CampbellLisa Rainey

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 homog...Continue Reading

Citations

Mar 24, 2020·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Madhura PatankarTuomo J Karttunen
Feb 1, 2019·Current Gastroenterology Reports·David G MenterScott Kopetz
Aug 27, 2019·Frontiers in Immunology·Szu-Han HuangR Brad Jones
Sep 27, 2021·The Journal of Pathology·Frederick Charles Campbell

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Methods Mentioned

BETA
GTPase
xenografting
nucleotide exchange

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