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Role Of Notch Signalling In Intestinal Stem Cell Renewal

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Related Experiment Video

Updated: Aug 30, 2025

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells

Published on: January 22, 2021

Acid Sphingomyelinase-Ceramide Induced Vascular Injury Determines Colorectal Cancer Stem Cell Fate.

Christy Li¹, Stefan Klingler¹, Sahra Bodo¹

¹Laboratory of Signal Transduction Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology

|August 29, 2022

Summary

Single dose radiotherapy effectively targets cancer stem cells by exploiting their dependence on homologous recombination repair. Enhancing this process converts resistant cells into sensitive ones, leading to tumor cure.

Keywords:

Colorectal Cancer; Acid Sphingomyelinase; Ceramide; Stem Cell Fate

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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres

Published on: July 22, 2020

Area of Science:

Oncology
Radiation Oncology
Cancer Stem Cell Biology

Background:

Cancer stem cells (CSCs) may possess unique treatment vulnerabilities compared to progeny.
Ultra-high single dose radiotherapy achieves higher cure rates (90-95%) than conventional fractionation (~65%).
Single dose radiotherapy activates microvascular acid sphingomyelinase/ceramide signaling, inducing a tumor SUMO Stress Response that inhibits homologous recombination repair (HRR).

Purpose of the Study:

To investigate if optimizing acid sphingomyelinase (ASM) dependent pathways enhances CSC-dependent tumor cure.
To explore the differential response of colorectal cancer stem cells to single dose radiotherapy.

Main Methods:

Utilized colorectal cancer patient-derived xenografts (PDXs) with varying Lgr5+ stem cell populations.
Assessed the radiosensitivity of microvasculature and stem cells in different PDX models.
Employed pharmacologic or gene therapy to enhance ASM/ceramide-mediated microvascular dysfunction during single dose radiotherapy.

Main Results:

Radioresistant PDX CLR27-2 exhibited resistant microvasculature and stem cells.
Radiosensitive PDX CLR1-1 showed sensitive microvasculature and stem cells.
Enhanced ASM/ceramide signaling sensitized radioresistant CLR27-2, making Lgr5+ cells the most sensitive population and achieving tumor cure.

Conclusions:

Homologous recombination repair (HRR) is a critical vulnerability in colorectal cancer stem cells.
Single dose radiotherapy, by targeting HRR, offers a potential therapeutic strategy for colorectal cancer stem cells.