TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3β dependent manner
Xinyu Jiang1, Wenfei Du1, Chenglong Yang1
1Key Laboratory of Precision Oncology in Universities of Shandong, Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.
Purpose:
Previous studies have shown that TBX21 (T-Box Transcription Factor 21) plays a vital role in coordinating multiple aspects of the immune response especially type 1 immune response as well as tumor progression. However, the function of TBX21 in colorectal cancer (CRC) remains unclear.
Methods:
IHC to investigate TBX21 expression in CRC tissues. Cell proliferation and apoptosis assays to validate TBX21 function in vitro and in vivo. RNA-seq assay to explore target genes of TBX21. Human phospho-kinase array assay to explore down-stream signaling of TBX21.
Results:
We disclosed that the expression of TBX21 was marked decreased in CRC versus normal tissue, and negatively correlated with CRC TNM stages. Surprisingly, we found that the CRC and normal cell lines show no TBX21 expression levels. Ectopic expression of TBX21 inhibited cell proliferation and promoted cell apoptosis in vitro. Moreover, RNA-sequence data first time showed that ARHGAP29 acts as the target gene of TBX21 to mediate down-stream signaling activation. Human phospho-kinase array data first time displayed that ectopic expression of TBX21 reduced kinase RSK and GSK3β activation. In contrast, knocked down the expression of TBX21 or ARHGAP29 alternatively abolished TBX21 mediated cell proliferation suppression, cell apoptosis enhancement and RSK/GSK3β activation. In addition, xenograft model studies demonstrated that TBX21 inhibits colorectal tumor progression via ARHGAP29/ RSK/ GSK3β signaling in vivo.
Conclusions:
In summary, the aforementioned findings suggest a model of TBX21 in suppressing CRC progression. This may provide a promising target for CRC therapy.
Insights
T-Box Transcription Factor 21 (TBX21) is decreased in colorectal cancer (CRC) and suppresses tumor progression by inhibiting proliferation and promoting apoptosis via the ARHGAP29/RSK/GSK3β pathway, offering a potential therapeutic target for CRC.
Area of Science:
- Immunology and Cancer Biology
- Molecular Oncology
Background:
- T-Box Transcription Factor 21 (TBX21) is implicated in immune responses and tumor progression.
- The specific role of TBX21 in colorectal cancer (CRC) has not been previously elucidated.
Purpose of the Study:
- To investigate the expression and function of TBX21 in colorectal cancer.
- To identify downstream targets and signaling pathways regulated by TBX21 in CRC.
Main Methods:
- Immunohistochemistry (IHC) for TBX21 expression in CRC tissues.
- In vitro and in vivo assays for cell proliferation and apoptosis.
- RNA-sequencing (RNA-seq) to identify TBX21 target genes.
- Human phospho-kinase array to analyze downstream signaling.
Main Results:
- TBX21 expression is significantly reduced in CRC tissues and negatively correlates with TNM stage.
- Ectopic TBX21 expression inhibits CRC cell proliferation and enhances apoptosis in vitro.
- TBX21 suppresses colorectal tumor progression in vivo via the ARHGAP29/RSK/GSK3β signaling pathway.
Conclusions:
- TBX21 acts as a tumor suppressor in colorectal cancer.
- The findings suggest TBX21 as a potential therapeutic target for CRC treatment.
Related Concept Videos
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Tumor Progression
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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal
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...
TGF - β Signaling Pathway
The Ras Gene
Ras is a...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...


