Related Experiment Video
Updated: May 3, 2026
A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
Published on: January 22, 2021
RSPO2-LGR5 signaling has tumour-suppressive activity in colorectal cancer
Changjie Wu1, Sunquan Qiu1, Liting Lu1
11] Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325000, China [2].
Abstract:
R-spondins are a family of secreted Wnt agonists. One of the family members, R-spondin 2 (RSPO2), has an important role in embryonic development, bone formation and myogenic differentiation; however, its role in human cancers remains largely unknown. Here we show that RSPO2 expression is downregulated in human colorectal cancers (CRCs) due to promoter hypermethylation, and that the RSPO2 reduction correlates with tumour differentiation, size and metastasis. Overexpression of RSPO2 suppresses CRC cell proliferation and tumorigenicity, whereas the depletion of RSPO2 enhances tumour cell growth. RSPO2 has an inhibitory effect on Wnt/β-catenin signaling in the CRC cells that show suppressed cell proliferation. In human CRC cells, the RSPO2-induced inhibition of Wnt signaling depends on leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5); RSPO2 interacts with LGR5 to stabilize the membrane-associated zinc and ring finger 3 (ZNRF3). Our data suggest that RSPO2 functions as a tumour suppressor in human CRCs, and these data reveal a RSPO2-induced, LGR5-dependent Wnt signaling-negative feedback loop that exerts a net growth-suppressive effect on CRC cells.
Insights
R-spondin 2 (RSPO2) acts as a tumor suppressor in colorectal cancers (CRCs). Its downregulation via promoter hypermethylation correlates with CRC progression, while RSPO2 re-expression inhibits tumor growth by modulating Wnt/β-catenin signaling.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- R-spondins are secreted Wnt agonists crucial for development.
- The role of R-spondin 2 (RSPO2) in human cancers, particularly colorectal cancers (CRCs), is largely unexplored.
- RSPO2 is known for its roles in embryonic development, bone formation, and myogenic differentiation.
Purpose of the Study:
- To investigate the role of RSPO2 in human colorectal cancers.
- To elucidate the mechanism by which RSPO2 affects CRC cell proliferation and tumorigenicity.
- To understand the relationship between RSPO2 expression, Wnt/β-catenin signaling, and CRC progression.
Main Methods:
- Analysis of RSPO2 expression in human colorectal cancer tissues.
- Assessment of RSPO2 promoter methylation status.
- In vitro studies involving RSPO2 overexpression and depletion in CRC cell lines.
- Investigation of Wnt/β-catenin signaling pathway activity.
- Examination of the interaction between RSPO2, LGR5, and ZNRF3.
Main Results:
- RSPO2 expression is significantly downregulated in human CRCs due to promoter hypermethylation.
- Reduced RSPO2 levels correlate with poorer tumor differentiation, larger tumor size, and metastasis.
- RSPO2 overexpression suppresses CRC cell proliferation and tumorigenicity.
- RSPO2 depletion enhances CRC cell growth.
- RSPO2 inhibits Wnt/β-catenin signaling in a LGR5-dependent manner by stabilizing ZNRF3.
Conclusions:
- RSPO2 functions as a tumor suppressor in human colorectal cancers.
- RSPO2 downregulation is a key event in CRC development and progression.
- A novel RSPO2-induced, LGR5-dependent negative feedback loop in Wnt signaling exerts a net growth-suppressive effect on CRC cells.
More Related Videos
06:24Author Spotlight: Liujunzi Decoction as a Traditional Chinese Treatment for Coloproctitis Cancer
Published on: October 13, 2023
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
03:03mTOR Signaling and Cancer Progression
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions