title: STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/Snail signaling.
abstract: The mammalian peptide hormone stanniocalcin 2 (STC2) plays an oncogenic role in many human cancers. However, the exact function of STC2 in human head and neck squamous cell carcinoma (HNSCC) is unclear. We aimed to examine the function and clinical significance of STC2 in HNSCC. Using in vitro and in vivo assays, we show that overexpression of STC2 suppressed cell apoptosis, promoted cell proliferation, migration, invasion, and cell cycle arrest at the G1/S transition. By contrast, silencing of STC2 inhibited these activities. We further show that STC2 upregulated the phosphorylation of AKT and enhanced HNSCC metastasis via Snail-mediated increase of vimentin and decrease of E-cadherin. These responses were blocked by silencing of STC2/Snail expression or inhibition of pAKT activity. Furthermore, clinical data indicate that high STC2 expression was associated with high levels of pAKT and Snail in tumor samples from HNSCC patients with regional lymph node metastasis (P < 0.01). Thus, we conclude that STC2 controls HNSCC metastasis via the PI3K/AKT/Snail signaling axis and that targeted therapy against STC2 may be a novel strategy to effectively treat patients with metastatic HNSCC.
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Duanshu
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liao
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Meng
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C114997:STC2 protein, human; D000071250:Snail Family Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: HNSCC; STC2; Snail; metastasis; pAKT