Abstract
BackgroundActivating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. However, the role of ATF2 in renal cell carcinoma (RCC) remains unclear.MethodsATF2 knockdown and overexpression studies were performed in RCC cells to evaluate changes in cell viability, cell cycle, apoptosis, migration and invasion. Xenograft models were used to examine the tumorigenic and metastatic capability of RCC cells upon ATF2 suppression. The expression of ATF2 in human RCC samples was determined using immunohistochemistry on a tissue microarray.ResultsATF2 knockdown in RCC cells reduced their proliferative and metastatic potentials, whereas ATF2 overexpression enhanced these properties. Mechanistic studies revealed that the transcription of CyclinB1, CyclinD1, Snail and Vimentin was directly regulated by ATF2 in RCC cells. Moreover, ATF2 was shown to be highly expressed in RCC tissues, especially in tumors with metastases. High expression of ATF2 correlated with aggressive clinico-pathological characteristics and predicted poor prognosis of RCC patients.ConclusionsATF2 exerts an oncogenic role in RCC and could serve as an important prognostic biomarker.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0383-2) contains supplementary material, which is available to authorized users.
Highlights
Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers
Right: the relative migration rate was calculated by dividing the change in the distance between the scratch edges by the initial distance. b & c Transwell assays were performed to evaluate cell migration following ATF2 knockdown (b), ATF2 overexpression (c) and control renal cell carcinoma (RCC) cells
Scale bar = 2 mm. d & e Transwell assays were performed to evaluate the invasion of ATF2 knockdown (d), ATF2 overexpression (e) and control RCC cells
Summary
Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. The role of ATF2 in renal cell carcinoma (RCC) remains unclear. Renal cell carcinoma (RCC) is the most prevalent malignancy of adult kidney, and its incidence has been increasing in recent decades [1, 2]. In response to extracellular stresses or inflammatory cytokines, the transcriptional activity of ATF2 is induced through Thr69- and/or Thr71phosphorylation by Jun N-terminal kinase (JNK) or p38 (MAPK14) [7,8,9]. In melanoma and non-small cell lung carcinoma, ATF2 acts as an important oncogene [10, 11], while in nonmalignant skin and breast cancer, ATF2 elicits tumor-suppressor function [12, 13], suggesting a contextdependent role for ATF2 in cancer biology
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