Retracted: Forkhead box protein k1 recruits TET1 to act as a tumor suppressor and is associated with MRI detection

Abstract

Objective: Today, more and more evidence suggests that Foxk proteins (Foxk1 and Foxk2) work as transcriptional repressors in different kinds of cancer, but whether Foxk1 has a role in mediating tumorigenesis in breast cancer, the evidence is rare. Methods: MCF-7 cells transfected with shFoxk1 displayed a mesenchymal morphology and reduced the expression of E-cadherin, and increased the expression of N-cadherin. Transwell invasion assay and living imaging assay show that the overexpression of Foxk1 could inhibit metastasis in vitro and in vivo. Ribonucleic acid sequencing revealed that the knockdown of Foxk1 resulted in the up-regulation of different oncogenes, which was implicated in metastasis and tumor angiopoiesis. Quantitative chromatin immunoprecipitation, chromatin immunoprecipitation and Luciferase reporter assays suggested that Foxk1 could bind to the promoter of epithelial-mesenchymal transition inducer Twist and vascular endothelial growth factor, VEGF. Mass Spectrometry, co-immunoprecipitation assays and glutathione-S-transferase pull-down assay detected that Foxk1 was physically associated with Ten-eleven translocation 1, TET1, in vivo and in vitro. Results: We reported that the mean expression level of Foxk1 in breast cancer was significantly lower than the adjacent noncarcinoma tissue. The higher Foxk1 expression was associated with better prognosis. Endothelial tube formation assays indicated that Foxk1 might regulate breast cancer angiogenesis through transcriptional repression of vascular endothelial growth factor. Furthermore, in vivo magnetic resonance imaging revealed the overexpression of Foxk1 could enhance the detection of the tumors. Further, a strong negative correlation was observed between Foxk1 and Twsit or between Foxk1 and vascular endothelial growth factor, and the higher Foxk1 expression is correlated with better over all survivals and better relapse-free survivals. Conclusions: Together, our data indicated the function of Foxk1 as a tumor suppressor in facilitating angiogenesis and metastasis in breast cancer.

Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

“…We show here that a significant portion of mutant ASXL1's function is linked to FOXK1 and FOXK2, as more than 60% of genes differentially regulated by C-terminal truncation mutant ASXL1 are direct targets of FOXK1/K2. Although both transcriptional activation (Sukonina et al, 2019) and repression (Sun et al, 2016;Li et al, 2019) can be regulated by FOXK1 and FOXK2, our study supports the overlapping and transcriptional activation role of FOXK1/K2 and is consistent with the gene silencing role of H2AK119 mono-ubiquitination mediated by the PR-DUB complex. Supporting this notion, knockdown of FOXK1/K2 or deletion of mutant ASXL1 allele leads to decreased H2AK119 monoubiquitination at the promoter regions of FOXK1/K2 target genes (Fig.…”

<p>Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy</p>

“…However, the exact role of the FOXK1 and FOXK2 in cancer is still controversial. In breast cancer, Sun et al 20 reported that FOXK1 expression is lower in cancer tissue and cell lines; on the contrary, In contrast, Li et al 19 showed that the expression of FOXK1 was higher in cancer tissue. Moreover, high FOXK1 expression has been reported in the tumor tissue compared with normal tissue in several cancers, including gastric, hepatoma, ovarian, esophagus, and colorectal cancers.…”

“…Moreover, the expression levels of the FOXK family members in cancers are still unclear. Sun et al 20 reported that FOXK1 expression is lower in breast cancer tissue and cell lines compared with normal tissue. In contrast, Li et al 19 showed that the expression of FOXK1 was higher in breast cancer tissue compared with adjacent-cancer tissues.…”

ISL1 is upregulated in breast cancer and promotes cell proliferation, invasion, and angiogenesis

“…In vitro tube formation analysis was performed using growth factor-reduced Matrigel (BD Biosciences), as previously described. 16 Briefly, a 200 μL growth factor-reduced Matrigel was coated in the 24-well plates and then solidified at 37°C for 30 minutes. HUVECs were cultured with CM from MCF-7 cells that were transfected with vector, ISL1 or SCR, siISL1.…”