B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related 
to advanced TNM stage and disease recurrence in oral squamous cell carcinoma 
(OSCC). However, the regulatory mechanism of BCL10 in OSCC progression is still 
unknown. Here, we showed that knockdown of endogenous BCL10 could significantly 
reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 
phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we 
identified S100P as a crucial downstream effector of BCL10-inhibited OSCC 
progression by high-throughput microarray analysis. S100P messenger RNA and 
protein expression levels were significantly diminished in silenced-BCL10 
clones, and transfected S100P expression plasmids restored migration, invasion, 
proliferation abilities and tumorigenicity in shBCL10 transfectants. 
Furthermore, we provided evidence that BCL10 regulated S100P expression through 
signal transducers and activators of transcription 1 (STAT1) and activating 
transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter 
activity, but showed no effect in truncated STAT1/ATF4 S100P promoter.  In 
addition, we also found that the P50/P65 signaling pathway was involved in 
BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could 
markedly reverse P65 activation via outside-in signaling. Taken together, we 
discovered a novel axis of BCL10-regulated OSCC progression via 
STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and 
will be beneficial for developing therapeutic strategy against advanced OSCC.