Related Experiment Video

Updated: Mar 28, 2026

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
06:38

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

Published on: January 22, 2021

7.0K

Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function

Elaine E Storm1, Steffen Durinck2, Felipe de Sousa e Melo1

  • 1Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.

Nature
|December 25, 2015
PubMed

Insights

Targeting RSPO3 in colorectal tumors with PTPRK-RSPO3 fusions inhibits growth and promotes differentiation. This approach targets cancer stem cells, offering a potential new therapy for colorectal cancer.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) is a significant health concern with many unmet therapeutic needs.
  • Genomic studies aim to identify CRC drivers for targeted therapy development.
  • Recurrent translocations in R-spondin genes were previously found in a subset of colorectal tumors.

Purpose of the Study:

  • To investigate the therapeutic potential of targeting RSPO3 in colorectal tumors harboring PTPRK-RSPO3 fusions.
  • To explore the role of intestinal stem cell compartments in driving PTPRK-RSPO3-driven colorectal tumor growth.

Main Methods:

  • Utilized human tumor xenografts from PTPRK-RSPO3-fusion-positive colorectal tumors.
  • Administered targeted anti-RSPO3 therapy.
  • Performed gene expression analysis to identify sensitive pathways.
  • Conducted functional assays to assess tumor response.

Main Results:

  • Targeting RSPO3 significantly inhibited tumor growth in PTPRK-RSPO3-fusion-positive xenografts.
  • RSPO3 inhibition promoted tumor cell differentiation.
  • Genes associated with intestinal stem cell compartments were highly sensitive to anti-RSPO3 treatment.

Conclusions:

  • RSPO3 is a key driver in a subset of colorectal tumors characterized by PTPRK-RSPO3 fusions.
  • Colorectal tumor growth is driven by a stem cell compartment.
  • Targeting cancer stem cell properties represents a promising therapeutic strategy for PTPRK-RSPO3-fusion-positive colorectal cancer.

More Related Videos

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres06:52

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

Published on: July 22, 2020

7.1K
In vitro Organoid Culture of Primary Mouse Colon Tumors07:33

In vitro Organoid Culture of Primary Mouse Colon Tumors

Published on: May 17, 2013

36.1K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.8K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
68
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.6K