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Untangling the complexities of micropapillary cancer †
Author(s) -
Charles Campbell Frederick
Publication year - 2021
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5809
Subject(s) - multicellular organism , colorectal cancer , cancer , biology , polarity (international relations) , morphology (biology) , phenotype , pathology , cancer research , microbiology and biotechnology , medicine , cell , gene , genetics
Abstract Distinct morphological subtypes of colorectal cancer (CRC) confer a bleak clinical outlook. In a recent issue of The Journal of Pathology , Onuma et al investigated morphological evolution of a highly fatal CRC subtype known as micropapillary cancer (MPC). This study enhances understanding of MPC biology including essential regulatory signals, cellular and multicellular phenotypes, as well as cancer behaviour. Iterative modelling in three‐dimensional (3D) patient‐derived CRC tissue‐originated spheroids (CTOSs) revealed spatiotemporal oscillations of Rho–ROCK hyperactivity underlying reversal of membrane polarity and suppression of lumen formation during development of multicellular MPC morphology. Corroborative studies in CTOSs, xenografts, and archival human CRCs confirm human disease relevance. Although cancer morphology has previously been considered irreversible, targeted inhibition of Rho–ROCK activity restored membrane polarity, lumenized multicellular assembly, and suppressed MPC morphology in 3D CTOS cultures and xenografts. Collectively, the study identifies molecular, biophysical, and multicellular mechanisms implicated in morphological evolution of micropapillary CRC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.