title: 12-O-tetradecanoylphorbol-13-acetate promotes breast cancer cell motility by increasing S100A14 level in a Kruppel-like transcription factor 4 (KLF4)-dependent manner.
abstract: The S100 protein family represents the largest subgroup of calcium binding EF-hand type proteins. These proteins have been reported to be involved in a wide range of biological functions that are related to normal cell development and tumorigenesis. S100A14 is a recently identified member of the S100 protein family and differentially expressed in a number of different human malignancies. However, the transcriptional regulation of S100A14 and its role in breast cancer needs to be further investigated. Here, we determined that 12-O-tetradecanoylphorbol-13-acetate (TPA) up-regulated the expression of KLF4 and facilitated its binding directly to two conserved GC-rich DNA segments within the S100A14 promoter, which is essential for the transactivation of KLF4 induced S100A14 expression. Furthermore, stable silencing of KLF4 significantly suppressed breast cancer cell migration induced by TPA. Collectively, these results offer insights into the fact that TPA provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner.
authors.affiliation: From the State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Chengshan
authors.initials: C
authors.lastname: Xu
authors.forename: Fang
authors.initials: F
authors.lastname: Ding
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhan
authors.forename: Jianlin
authors.initials: J
authors.lastname: Ma
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Shi
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Qu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002135:Calcium-Binding Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C462950:S100A14 protein, human; D013755:Tetradecanoylphorbol Acetate
keywords: Breast Cancer; Cell Motility; Gene Regulation; Kruppel-like Factor (KLF); S100 Proteins; TPA