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Updated: Jan 15, 2026
The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior
Published on: June 12, 2019
Selenium-binding protein 1 suppresses tumor invasion by destabilizing MMP2 mRNA through a p21-dependent AUF1-ARE
Yulei Wang1, Wenhang Lin1, Yixuan Liao1
1Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Abstract:
Selenium-binding protein 1 (SELENBP1) is frequently downregulated across multiple human solid tumors and has long been recognized as a tumor suppressor. Our previous work established that SELENBP1 restrained cell-cycle progression by transcriptionally inducing p21 (CDKN1A) through a p53-independent pathway, yet the molecular basis of its anti-invasive function remained unclear. Here, using bladder and colon cancer cell models with stable SELENBP1 overexpression, we show that SELENBP1 markedly inhibits cellular invasion without affecting migration, accompanied by a selective downregulation of matrix metalloproteinase 2 (MMP2). Mechanistic analyses revealed that SELENBP1 destabilizes MMP2 mRNA via its 3'-untranslated region (3'-UTR). Further, SELENBP1 upregulates the AU-rich element (ARE)-binding protein AUF1, which in turn accelerates MMP2 mRNA decay in an ARE-dependent manner. Silencing AUF1 abolished SELENBP1-mediated repression of MMP2 and restored invasive capacity, demonstrating that AUF1 is a critical mediator in this process. Importantly, we also identified p21 as an indispensable upstream regulator: SELENBP1 induced AUF1 and repressed MMP2 only in the presence of functional p21, whereas p21-deficient cells failed to transmit this regulatory cascade. Together, our findings delineate a previously unrecognized SELENBP1-p21-AUF1-MMP2 axis that links SELENBP1-mediated invasion suppression to post-transcriptional control of extracellular matrix remodeling. This study highlights SELENBP1 as a multifunctional tumor suppressor and suggests that restoring this pathway may offer therapeutic opportunities in invasive cancers.
Insights
Selenium-binding protein 1 (SELENBP1) suppresses cancer invasion by destabilizing MMP2 mRNA through a p21- and AUF1-dependent pathway. Restoring this SELENBP1 axis may offer new therapeutic strategies for invasive cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Selenium-binding protein 1 (SELENBP1) is a known tumor suppressor downregulated in many solid tumors.
- Previous studies showed SELENBP1 restrains cell-cycle progression via p21 induction.
- The molecular mechanisms underlying SELENBP1's anti-invasive function were previously unclear.
Purpose of the Study:
- To elucidate the molecular basis of SELENBP1's anti-invasive function.
- To identify the key molecular players involved in SELENBP1-mediated invasion suppression.
- To investigate the role of SELENBP1 in regulating extracellular matrix remodeling.
Main Methods:
- Stable SELENBP1 overexpression in bladder and colon cancer cell models.
- Analysis of cellular invasion, migration, and matrix metalloproteinase 2 (MMP2) expression.
- Investigation of MMP2 mRNA destabilization mechanisms, including 3'-untranslated region (3'-UTR) interactions.
- Assessment of AU-rich element (ARE)-binding protein AUF1's role and p21 dependency.
Main Results:
- SELENBP1 overexpression inhibited cellular invasion and selectively downregulated MMP2.
- SELENBP1 destabilizes MMP2 mRNA via its 3'-UTR and upregulates AUF1.
- AUF1 mediates SELENBP1-induced MMP2 repression in an ARE-dependent manner.
- The SELENBP1-mediated pathway requires functional p21.
Conclusions:
- A novel SELENBP1-p21-AUF1-MMP2 signaling axis was identified, linking SELENBP1 to post-transcriptional regulation of MMP2.
- SELENBP1 acts as a multifunctional tumor suppressor by inhibiting invasion through this pathway.
- This pathway represents a potential therapeutic target for invasive cancers.
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