title: Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishiguchi
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Fujiwara
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.|Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Kurihara
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.affiliation: Institute for Biochemistry, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Anja Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D018450:Disease Progression; D018572:Disease-Free Survival; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D016016:Proportional Hazards Models; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins
keywords: MIA; STOX2; metastasis; multidrug resistance; oral cancer