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Updated: Aug 24, 2026
A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
Published on: January 22, 2021
Functional Smoothened is required for expression of GLI3 in colorectal carcinoma cells
Yanhua Zhu1, Roberta M James, Audrey Peter
1Sir Alastair Currie Cancer Research UK Laboratories, Division of Pathology, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
Abstract:
We investigated a role for Hedgehog signalling in colon cancer by studying transcription of members of the pathway in human colorectal carcinoma cell lines. We determined the methylation status and screened the gene encoding the Hedgehog receptor-associated protein Smoothened (SMO) for putative mutations. In three cell lines lacking SMO expression the SMO promoter was fully methylated and the transcription factor GLI3 was not expressed. Two additional cell lines both having one methylated SMO allele and expressing mutant SMO did not express GLI3. Our results suggest that expression of wild-type SMO is required for expression of GLI3 by a mechanism that is independent of conventional Hedgehog signalling.
Insights
Hedgehog signaling plays a role in colon cancer. Wild-type Smoothened (SMO) expression is necessary for GLI3 expression, independent of standard Hedgehog pathways.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hedgehog signaling is implicated in various cancers, including colorectal carcinoma.
- Understanding the molecular mechanisms of Hedgehog pathway dysregulation in colon cancer is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role of Hedgehog signaling in human colorectal carcinoma cell lines.
- To determine the transcriptional status and genetic alterations of key Hedgehog pathway components, specifically Smoothened (SMO).
Main Methods:
- Analysis of Hedgehog pathway gene transcription in colorectal cancer cell lines.
- Assessment of SMO gene promoter methylation status.
- Screening of the SMO gene for mutations.
Main Results:
- Three cell lines exhibited absent SMO expression due to full SMO promoter methylation and lacked GLI3 expression.
- Two cell lines with one methylated SMO allele and mutant SMO also failed to express GLI3.
- These findings suggest a correlation between SMO status and GLI3 expression.
Conclusions:
- Wild-type SMO expression appears to be a prerequisite for GLI3 expression in these colon cancer models.
- This regulatory mechanism may operate independently of the canonical Hedgehog signaling cascade.
- Further research is warranted to elucidate this novel SMO-GLI3 interaction in colon cancer.
