STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/Snail signaling
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Shuwen Yang1,2,3,*, Qinghai Ji1,2,3,*, Bin Chang2,4, Yan Wang2,3, Yongxue Zhu1,2, Duanshu Li1,2, Caiping Huang1,2, Yulong Wang1,2, Guohua Sun1,2, Ling Zhang1,2, Qing Guan1,2, Jun Xiang1,2, Wenjun Wei1,2, Zhongwu Lu1,2, Tian Liao1,3, Jiao Meng3, Ziliang Wang3, Ben Ma1,2,3, Li Zhou1,2,3, Yu Wang1,2,3, Gong Yang2,3,5
1Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
3Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China
4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
5Central Laboratory, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China
Yu Wang, email: email@example.com
Gong Yang, email: firstname.lastname@example.org
Keywords: STC2, pAKT, Snail, HNSCC, metastasis
Received: May 23, 2016 Accepted: October 14, 2016 Published: November 15, 2016
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.
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