Endogenous PROM1 activation redistributes liver cancer cells along a preexisting differentiation axis
- 1Institute of Pathology, University of Regensburg, Regensburg, Germany
Abstract
CD133 is widely used as a marker of stem-like cells in hepatocellular carcinoma, yet its functional contribution remains incompletely defined. In PLC/PRF/5 cells, acute CRISPR activation of endogenous PROM1 suppresses hepatic programs, whereas PROM1 knockdown elicits an opposing hepatocyte-identity response, together defining a PROM1-responsive transcriptional axis. Single-cell profiling shows that this axis is preexisting and tracks endogenous PROM1 heterogeneity, separating a hepatocyte-like, PROM1-low compartment from a PROM1-enriched, less hepatocyte-like compartment. Sustained PROM1 activation reduces the hepatocyte-like compartment and shifts the population toward intermediate positions along this axis. Related transcriptional patterns are detectable in an independent HuH-7 dataset and a human HCC case. Endogenous ALFA tagging identifies candidate CD133-associated proteins. Together, these findings support CD133 as an active contributor to tumor-cell state redistribution, extending its role beyond a mere marker of stem-like populations.
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BibTeX
@misc{schneider2026endogenous,
title = {{Endogenous PROM1 activation redistributes liver cancer cells along a preexisting differentiation axis}},
author = {T. Schneider and K. Kaneko and M. Vogl and K. Utpatel and A. Immel and D. Hirsch and C. Raggi and E. Spinola Lasso and M. Evert and G.-S. Feng and D. F. Calvisi and A. Scheiter},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.01.763386},
url = {https://www.biorxiv.org/content/10.64898/2026.11.01.763386v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Endogenous PROM1 activation redistributes liver cancer cells along a preexisting differentiation axis
AU - T. Schneider
AU - K. Kaneko
AU - M. Vogl
AU - K. Utpatel
AU - A. Immel
AU - D. Hirsch
AU - C. Raggi
AU - E. Spinola Lasso
AU - M. Evert
AU - G.-S. Feng
AU - D. F. Calvisi
AU - A. Scheiter
PY - 2026
DA - 2026/11/01
PB - bioRxiv
DO - 10.64898/2026.11.01.763386
UR - https://www.biorxiv.org/content/10.64898/2026.11.01.763386v1
AB - CD133 is widely used as a marker of stem-like cells in hepatocellular carcinoma, yet its functional contribution remains incompletely defined. In PLC/PRF/5 cells, acute CRISPR activation of endogenous PROM1 suppresses hepatic programs, whereas PROM1 knockdown elicits an opposing hepatocyte-identity response, together defining a PROM1-responsive transcriptional axis. Single-cell profiling shows that this axis is preexisting and tracks endogenous PROM1 heterogeneity, separating a hepatocyte-like, PROM1-low compartment from a PROM1-enriched, less hepatocyte-like compartment. Sustained PROM1 activation reduces the hepatocyte-like compartment and shifts the population toward intermediate positions along this axis. Related transcriptional patterns are detectable in an independent HuH-7 dataset and a human HCC case. Endogenous ALFA tagging identifies candidate CD133-associated proteins. Together, these findings support CD133 as an active contributor to tumor-cell state redistribution, extending its role beyond a mere marker of stem-like populations.
ER -