The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.

Abstract

BACKGROUND:

Loss of STAT1 (Signal Transducer and Activator of Transcription-1) has been implicated in the pathobiology of a number of cancer types. Nonetheless, the biological and clinical significance of STAT1 in esophageal squamous cell carcinomas (ESCC) has not been comprehensively studied.

METHODS:

Using immunohistochemistry, we detected the STAT1 expression in a cohort of ESCC patients; In-vitro experiments, we used enforced gene transfection of STAT1C into two STAT1- weak/negative ESCC cell lines and siRNA knockdown of STAT1 in two STAT1-strong ESCC cell lines to detect STAT1 function in ESCC.

RESULTS:

We found that the expression of STAT1 was heterogeneous in ESCC, with 64 (49.0%) strongly positive cases, 59 (45.0%) weakly positive cases and 8 (6.1%) negative cases. STAT1 expression inversely correlated with the depth of tumor invasion and tumor size (p=0.047 and p=0.029, respectively, Chi square). Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019). In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011). Our in-vitro experiments revealed that STAT1 is proapoptotic and inhibitory to cell-cycle progression and colony formation. Lastly, we found evidence that STAT1 signaling in ESCC cells down-regulated the expression and/or activity of NF-κB and STAT3, both of which are known to have oncogenic potential.

CONCLUSION:

To conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC. Loss of STAT1, which is frequent in ESCC, contributes to the pathogenesis of these tumors.

• Authors: Ying Zhang, Ommoleila Molavi, Min Su, Raymond Lai
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 791 (Oct 29 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 25355139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• STAT1 Transcription Factor
• STAT1 protein, human
• STAT3 Transcription Factor
• STAT3 protein, human

Topics

• Adult
• Aged
• Apoptosis (genetics)
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Cycle Checkpoints (genetics)
• Cell Line, Tumor
• Down-Regulation (genetics)
• Esophageal Neoplasms (genetics, metabolism, pathology)
• Female
• Humans
• Male
• Middle Aged
• NF-kappa B (genetics, metabolism)
• Neoplasm Invasiveness
• STAT1 Transcription Factor (genetics, metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• Survival Rate
• Transcription, Genetic
• Tumor Stem Cell Assay