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 language | English |
|---|---|
| Journal | Journal of Pathology |
| Early online date | 26 Sept 2021 |
| DOIs | |
| Publication status | Early online date - 26 Sept 2021 |
Keywords
- Pathology and Forensic Medicine
Access to Document
- Untangling the complexities of micropapillary cancer
© 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.