title: Inhibition of Foxp3 in cancer cells induces apoptosis of thyroid cancer cells.
abstract: Foxp3+ regulatory T cells (Tregs) in lymphocytes facilitate the thyroid tumor growth and invasion. Very limited information is available on Foxp3 expression in thyroid cancer cells and its function is totally unknown. This study demonstrated that Foxp3 expression was increased in thyroid cancer cells. Inhibition of Foxp3 decreased cell proliferation and migration, but increased apoptosis, suggesting a positive role of Foxp3 in cancer growth. Interestingly, Foxp3 inhibition enhanced PPARγ expression and activity. In addition, Foxp3 inhibition downregulated NF-κB subunit p65 and cyclin D1 but upregulated caspase-3 levels. These molecular changes are in line with Foxp3 shRNA-mediated alteration of cell functions. Collectively, our study demonstrates that thyroid cancer cells express a high level of functional Foxp3 and that the inhibition of the Foxp3 suppresses the proliferation and migration but promotes apoptosis, suggesting that targeting Foxp3 in thyroid cancer cells may offer a novel therapeutic option for thyroid cancer.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Ryan
authors.initials: R
authors.lastname: Chu
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Shirley Y W
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Vlantis
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: C Andrew
authors.initials: CA
authors.lastname: van Hasselt
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Enders K W
authors.initials: EK
authors.lastname: Ng
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Michael Dahua
authors.initials: MD
authors.lastname: Fan
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Ng
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Amy B W
authors.initials: AB
authors.lastname: Chan
authors.affiliation: Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.affiliation: Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. Electronic address: gchen@cuhk.edu.hk.
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D009363:Neoplasm Proteins / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D047495:PPAR gamma; C498143:RELA protein, human; D051996:Transcription Factor RelA; D019938:Cyclin D1
keywords: Apoptosis; Foxp3; PPARγ; Thyroid cancer