Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression

鹳头盒 2 和黑色素瘤抑制活性促进口腔鳞状细胞癌进展

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作者:Tomonori Sasahira, Yukiko Nishiguchi, Rina Fujiwara, Miyako Kurihara, Tadaaki Kirita, Anja Katrin Bosserhoff, Hiroki Kuniyasu

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.

Conclusions

Our results suggest that MIA-STOX2 signaling may be a useful diagnostic and therapeutic target in OSCCs.

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.

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