Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression.
BACKGROUND
Storkhead box protein 2 (STOX2) is a transcriptional factor associated with pre-eclampsia with fetal growth restriction. We recently reported that melanoma inhibitory activity (MIA) promotes oral squamous cell carcinoma (OSCC) progression. However, the relationship between STOX2 and MIA remains unknown in malignancies.


METHODS
We used immunohistochemistry and PCR to investigate MIA and STOX2 expression in OSCC. We also performed functional analysis in human OSCC cells.


RESULTS
MIA and STOX2 mRNA levels were higher in OSCCs than in normal oral epithelial cells, and upregulation of STOX2 was significantly correlated with overexpression of MIA. Immunostaining for STOX2 was associated with nodal metastasis (P = 0.0002) and MIA expression (P < 0.0001). Furthermore, MIA expression (P = 0.0035) and STOX2 expression (P = 0.0061) were associated with poor outcome in OSCCs. In vitro analysis using OSCC cells revealed that MIA increased expression of STOX2 by paracrine manner. Moreover, STOX2 accelerated OSCC cell growth, invasion, suppressed apoptosis, and enhanced resistance to paclitaxel, cisplatin, and 5-FU.


CONCLUSIONS
Our results suggest that MIA-STOX2 signaling may be a useful diagnostic and therapeutic target in OSCCs.
['Sasahira|Tomonori|T|', 'Nishiguchi|Yukiko|Y|', 'Fujiwara|Rina|R|', 'Kurihara|Miyako|M|', 'Kirita|Tadaaki|T|', 'Bosserhoff|Anja Katrin|AK|', 'Kuniyasu|Hiroki|H|']
D000328:Adult D000368:Aged D014408:Biomarkers, Tumor D002294:Carcinoma, Squamous Cell D002352:Carrier Proteins D018450:Disease Progression D018572:Disease-Free Survival D016326:Extracellular Matrix Proteins D005260:Female D006258:Head and Neck Neoplasms D006801:Humans D053208:Kaplan-Meier Estimate D008297:Male D008875:Middle Aged D009062:Mouth Neoplasms D009363:Neoplasm Proteins D016016:Proportional Hazards Models D000077195:Squamous Cell Carcinoma of Head and Neck
STOX2 MIA metastasis multidrug resistance oral cancer