Untangling the complexities of micropapillary cancer

Frederick Charles Campbell

Research output: Contribution to journalArticlepeer-review

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 (CTOS) 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 CTOS, 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.
Original languageEnglish
JournalJournal of Pathology
Early online date26 Sep 2021
DOIs
Publication statusEarly online date - 26 Sep 2021

Keywords

  • Pathology and Forensic Medicine

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