TCF4/β‑catenin complex is directly upstream of FGF21 in mouse stomach cancer cells

Abstract

Abstract. Fibroblast growth factor 21 (FGF21) as a member of the FGFs serves a key role in glucose homeostasis and protection of the liver, heart, kidney and skin from damage as well as cancer cell development. In addition, transcription of FGF21 is sensitive to diverse damages; however, the role of the transcriptional regulator of FGF21 in cancer cells remains to be elucidated. FGFs were identified to have dominant expression in cancer cells; therefore, mouse forestomach carcinoma (MFC) cells were used in the present study, which is a mouse stomach cancer cell strain for identifying the FGF21 regulators. In promoter analysis of FGF21, the putative transcription factor 4 (TCF4) binding motifs ( T / A C / G AAAG) were observed within 1.5 kb of the promoter region. Further chromatin immunoprecipitation and yeast-one hybrid assays identified that TCF4 directly bound to one of the two putative binding motifs observed. A co-immunoprecipitation assay identified that β-catenin interacts with TCF4 in MFC cells, and the β-catenin/TCF4 complex bound to the promoter of FGF21. In order to examine the function of TCF4 and β-catenin in transcriptional regulation of FGF21, TCF4 and β-catenin was transiently expressed in MFC cells. Reverse transcription-quantitative polymerase chain reaction results revealed that overexpression of TCF4 and β-catenin activated FGF21 transcription. Besides, suppression of β-catenin via a specific short interfering RNA resulted in reduction of FGF21 expression. Together these findings suggest that the β-catenin/TCF complex directly activates FGF21 via promoter binding. The observations of the present study may help elucidate the regulatory mechanism of FGF21, which is a key pharmaceutical protein.

Hsa_circ_0016070/micro‐340‐5p Axis Accelerates Pulmonary Arterial Hypertension Progression by Upregulating TWIST1 Transcription Via TCF4/β‐Catenin Complex

“… 43 In addition, the TCF4/β‐catenin transcription complex also affected the transcription of a large number of genes, such as c‐Myc, 44 Cyclin D1, 45 and Bcl‐2. 46 These downstream targeted genes were confirmed to be involved in the occurrence and development of PH. 47 , 48 , 49 Moreover, LF3 (an inhibitor of the interaction between TCF4 and β‐catenin) inhibited the progression of PH.…”

T Cell Factor 4 Is Involved in Papillary Thyroid Carcinoma via Regulating Long Non-Coding RNA HCP5

“…TCF4 has been observed to directly bind to 1.5 kb of the promoter region of FGF21 in stomach cancer cells. 27 TCF4/β-catenin complex can bind to 1.5 kb of the Smo and Gli1 promoters in human fibroblasts. 28 Despite of the regulatory function of target proteins expression, TCF4 can regulate lncRNAs expression.…”

Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways

“…T-cell factor/lymph enhancer factor-1 (TCF/LEF1) is a transcription complex that mediates the transcription of genes triggered by classic Wnt pathway. When the Wnt pathway is activated, b-catenin can bind to the TCF/ LEF1 complex by translocating into the nucleus and bind to the target gene DNA to initiate the transcription of related genes, such as: cyclinD1, c-Myc, MMPs (62)(63)(64)(65)(66). Wnt/b-catenin plays a vital role in tumor occurrence and treatment response.…”