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S1P Lyase siRNA Dampens Malignancy of DLD-1 Colorectal Cancer Cells
Wajiha Farha Faqar-Uz-Zaman1, Katrin G Schmidt1, Dominique Thomas2
1Institute of General Pharmacology and Toxicology, Pharmazentrum Frankfurt/ZAFES, Hospital of the Goethe University, Frankfurt am Main, Germany.
Abstract:
Sphingosine-1-phosphate lyase 1 (S1P lyase or SGPL1) is an essential sphingosine-1-phosphate-degrading enzyme. Its manipulation favors onset and progression of colorectal cancer and others in vivo. Thus, SGPL1 is an important modulator of cancer initiation. However, in established cancer, the impact of retrospective SGPL1 modulation is elusive. Herein, we analyzed how SGPL1 siRNA affects malignancy of the human colorectal cancer cells DLD-1 and found that in parallel to the reduction of SGPL1 expression levels, migration, invasion, and differentiation status changed. Diminished SGPL1 expression was accompanied with reduced cell migration and cell invasion in scratch assays and transwell assays, whereas metabolic activity and proliferation was not altered. Decreased migration was attended by increased cell-cell-adhesion through upregulation of E-cadherin and formation of cadherin-actin complexes. Spreading cell islets showed lower vimentin abundance in border cells. Furthermore, SGPL1 siRNA treatment induced expression of epithelial cell differentiation markers, such as intestinal alkaline phosphatase and cytokeratin 20. Hence, interference with SGPL1 expression augmented a partial redifferentiation of colorectal cancer cells toward normal colon epithelial cells. Our investigation showed that SGPL1 siRNA influenced tumorigenic activity of established colorectal cancer cells. We therefore suggest SGPL1 as a target for lowering malignant potential of already existing cancer.
Insights
Sphingosine-1-phosphate lyase 1 (SGPL1) reduction in colorectal cancer cells decreased migration and invasion. This suggests SGPL1 is a potential target for reducing the malignant potential of established cancers.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Sphingosine-1-phosphate lyase 1 (SGPL1) degrades sphingosine-1-phosphate, a key lipid mediator.
- SGPL1 dysregulation is implicated in cancer initiation and progression.
- The role of SGPL1 in established cancers remains largely unexplored.
Purpose of the Study:
- To investigate the effect of SGPL1 knockdown on the malignancy of established human colorectal cancer cells (DLD-1).
- To determine if modulating SGPL1 can alter the tumorigenic potential of existing colorectal cancers.
Main Methods:
- Utilized small interfering RNA (siRNA) to reduce SGPL1 expression in DLD-1 cells.
- Performed scratch and transwell assays to assess cell migration and invasion.
- Analyzed cell-cell adhesion molecules (E-cadherin), intermediate filaments (vimentin), and epithelial differentiation markers (intestinal alkaline phosphatase, cytokeratin 20).
Main Results:
- SGPL1 siRNA significantly reduced cell migration and invasion without affecting metabolic activity or proliferation.
- Reduced SGPL1 expression led to increased cell-cell adhesion via E-cadherin upregulation and cadherin-actin complex formation.
- SGPL1 knockdown induced the expression of epithelial differentiation markers, indicating partial redifferentiation towards normal colon epithelial cells.
Conclusions:
- SGPL1 siRNA treatment influences the tumorigenic activity of established colorectal cancer cells.
- Targeting SGPL1 represents a potential therapeutic strategy for reducing the malignant potential of existing colorectal cancers.
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