STAT3 Promotes Invasion and Aerobic Glycolysis of Human Oral Squamous Cell Carcinoma via Inhibiting FoxO1
Authors: Ke Wang
Min Zheng
Ya-Ling Tang
Sha-Sha Wang
Xiang-Hua Yu
Ya-Jie Tang
Hao-Fan Wang
Ming-Xin Cao
Xin-Hua Liang
Li Li
Journal: Frontiers in Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: EMT; FoxO1; OSCC; STAT3; aerobic glycolysis.
Affiliations: Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China., State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China., State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China., State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Abstract:  Signal transducer and activator of transcription 3 (STAT3), a previously accepted tumor-promoting protein in various malignancies, plays a key role in the process of cancer glycolysis. However, the role and potential mechanism of STAT3 in aerobic glycolysis and progression of oral squamous cell carcinoma (OSCC) has not been explored. In the present study, we demonstrated that STAT3 knockdown remarkably inhibited migration, invasion, expressions of epithelial-mesenchymal transition (EMT) markers, and aerobic glycolysis of OSCC cells by up-regulation of FoxO1. Consistently, the expression of nuclear Tyr705-phosphorylated STAT3, an active form of STAT3, was significantly elevated in OSCC tissues compared with adjacent normal tissues, and increased nuclear staining of Tyr705-phosphorylated STAT3 was associated with metastasis and shorter overall survival. Moreover, FoxO1, which was also mainly expressed in OSCC specimens, decreased in poorly-differentiated tissues compared with the relatively well-differentiated ones, and inversely correlated with the expression of nuclear Tyr705-phosphorylated STAT3 from patients with OSCC. Hence, our findings collectively characterized the contributing role of STAT3/FoxO1 in invasion and aerobic glycolysis of OSCC cells, which may lead to the worse clinical outcome. 

Retracted: Yes

PubPeer comments:
 This paper is based on some notions (e.g., Definition 1 and Definition 2) from Wei et al (2017, doi: 10.3233 jifs-16715), which was published in 2017 by the second author G.W. Wei of this paper and his co-authors and retracted in 2019. The method based on Definition 1 and Definition 2 is not sound according to the comment on https: pubpeer.com publications 93B929BEBF4CA47902A671C6DE4CD7 See also https: pubpeer.com publications AA9FBE699FCCDE4826CB1E3CDAC1C4 https: pubpeer.com publications C0FC614C6534509B54E58AD28E1298 https: pubpeer.com publications 9B775D7555967DCAAA7AF174019964 https: pubpeer.com publications 9E98AAE6D8F2CC8435A5C3A6BB4A50 https: pubpeer.com publications A831A7FF4543567D2644CEF6EC4395 https: pubpeer.com publications 1390E350BE5697BC796BFD2DA4BBA6 https: pubpeer.com publications 4A9C06FB0A56F985177089526C3F29 https: pubpeer.com publications 559482832A25EB877EF47ACCA464D8 https: pubpeer.com publications E9163FAD04D8C6B2D1BFB7B5E6F576 https: pubpeer.com publications FC53E9C21E8CE832C4186EDDFDFC27 https: pubpeer.com publications 13CE8C163C376B797841046DE2B46B https: pubpeer.com publications FAE24E6C38326C60F3EE601F6D0C1A https: pubpeer.com publications 6714C6C2D8100E026807E2746B0B4B https: pubpeer.com publications E782F6998414AF6DB7B9FE16BCEBDA   ,