Research by Niki Chalkidi and Athanasia Stavropoulou at the Koliaraki Lab reveals that Notch3 regulates pericyte phenotypic plasticity in colorectal cancer.
Pericytes—cells that wrap around blood vessels—undergo significant changes within tumors, but the molecular signals controlling these alterations have remained elusive. The new study by Chalkidi, Stavropoulou et al reveals that Notch3 signaling acts as a master switch governing pericyte behavior in colorectal cancer.
Using genetic manipulation in mouse models, Chalkidi, Stavropoulou et al showed that activating Notch3 drives pericyte proliferation while suppressing their contractile function, ultimately compromising blood vessel integrity. Conversely, deleting Notch3 normalized the tumor vasculature and significantly reduced the development of advanced tumors. Single-cell RNA sequencing analysis of both mouse and human CRC samples further confirmed distinct pericyte subpopulations defined by their Notch3 activity status.
These findings establish Notch3 as a critical regulator of pericyte phenotypic switching and suggest that targeting this pathway could offer a promising therapeutic strategy through vascular normalization.
Reference:
Chalkidi N, Stavropoulou A, Arvaniti VZ, Paraskeva C, Monogyiou A, Sakkou M, Nikolaou C, Koliaraki V. Notch3 regulates pericyte phenotypic plasticity in colorectal cancer. Commun Biol. 2026 Jan 30. doi: 10.1038/s42003-026-09629-4.