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Thioredoxin-like protein 2 is overexpressed in colon cancer and promotes cancer cell metastasis by interaction with ran.


ABSTRACT:

Aims

Our previous work identified thioredoxin-like protein 2 (Txl-2) as the target of the monoclonal antibody MC3 associated with colon cancer, but its underlying mechanisms remain poorly understood. Txl-2, a novel thioredoxin (Trx) and nucleoside diphosphate kinase family member, is alternatively spliced and gives rise to three different Txl-2 isoforms. In this study, Txl-2 expression in colon cancer, differential functions for Txl-2 isoforms in cell invasion and metastasis, and the downstream signaling were investigated.

Results

Txl-2 expression was elevated in colon cancer tissues compared to normal colonic tissues, with a high correlation between the histological grade and prognosis. Knockdown of Txl-2 expression significantly inhibited cancer cell motility, and the invasive and metastatic abilities of colon cancer cells. Interestingly, Txl-2 isoforms showed differential effects on cancer cell invasion and metastasis. Cell invasion and metastasis were significantly promoted by Txl-2b but inhibited by Txl-2c, while no obvious effect was observed for Txl-2a. Furthermore, a direct interaction was identified between Txl-2b and Ran, a Ras-related protein, by yeast two-hybrid assay and coimmunoprecipitation. PI3K pathway was found to be a major pathway mediating Txl-2b induced tumor invasion and metastasis.

Innovation

The current study provides a novel biomarker and target molecule for the diagnosis and treatment of colon cancer and provides a novel paradigm to understand how alternative splicing functions in human cancer.

Conclusion

Our findings demonstrate an elevated Txl-2 expression in colon cancer and that Txl-2b promotes cell invasion and metastasis through interaction with Ran and PI3K signaling pathway.

SUBMITTER: Lu Y 

PROVIDER: S-EPMC3763228 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

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