Browsing by Subject "Transcription factor"

Now showing 1 - 4 of 4
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    BATF is involved in the malignant phenotype and epithelial-mesenchymal transition of colon cancer cells via ERK/PD-L1 signaling
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Chen, Xiaoqiong; Dong, Huaqian; Jin, Liping
    Objective. Transcription factors have emerged as primary regulators in colon cancer. Basic Leucine Zipper Transcription Factor (BATF) was found to be differentially expressed in colon cancer. This study aimed to explore the impact of BATF on the malignant phenotype and epithelial-mesenchymal transition (EMT) process. Methods. Based on The Cancer Genome Atlas (TCGA) data, the correlation between BATF and patients’ overall prognosis was analyzed. BATF expression in epithelial and colon cancer cells was evaluated. By knocking down its levels in colon cancer cells, its effects on the malignant phenotype, apoptosis, EMT progression, and ERK/PD-L1 were evaluated. Cells were treated with ERK/PD-L1 agonists, and the BATF cell regulation was re-examined. Results. BATF levels were negatively correlated with patients’ overall survival. BATF is upregulated in colon cancer cell lines, and BATF knockdown in HCT116 cells suppressed the malignant cellular phenotypes (proliferation, migration, and invasion) and increased apoptosis. BATF knockdown inhibited EMT and ERK/PD-L1 signaling activation, whereas upon agonist treatment, BATF potency was disrupted. Conclusion. This study revealed that BATF is involved in the malignant phenotype and EMT of colon cancer cells, and this process may be mediated by ERK/PD-L1 signaling
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    BRN2 is a non-canonical melanoma tumor-suppressor
    (Springer Nature, 2021-06-17) Hamm, Michael; Sohier, Pierre; Petit, Valérie; Raymond, Jérémy H.; Delmas, Véronique; Le Coz, Madeleine; Gesbert, Franck; Kenny, Colin; Aktary, Zackie; Pouteaux, Marie; Rambow, Florian; Sarasin, Alain; Charoenchon, Nisamanee; Bellacosa, Alfonso; Mosteo, Laura; Lauss, Martin; Meijer, Dies; Steingrimsson, Eirikur; Jönsson, Göran B.; Cornell, Robert; Davidson, Irwin; Goding, Colin R.; Larue, Lionel; Sánchez del Campo Ferrer, Luis; Bioquímica y Biología Molecular A
    While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600E PtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression
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    E2F1-induced upregulation of TROAP contributes to endometrial cancer progression
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Wang, Shanshan; Sun, Yidan; Guo, Minjing; Zhu, Ping; Xin, Beibei
    Purpose. To investigate the role of Trophinin-associated protein (TROAP) in endometrial cancer (EC) progression and elucidate how the transcription factor E2F transcription factor 1 (E2F1) modulates EC by upregulating TROAP expression. Methods. TROAP expression in EC tissues and cell lines was analyzed using bioinformatics databases, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry. TROAP was knocked down in EC cells to assess its effects on proliferation, migration, invasion, and glycolysis. Potential transcription factors regulating TROAP were identified, and the relationship between E2F1 and TROAP gene regulation was examined using dual luciferase assay. In vivo tumor growth was evaluated using a mouse xenograft model. Results. TROAP was overexpressed in EC tissues and cell lines compared with normal controls. High TROAP expression correlated with poor differentiation, advanced stage, lymph node metastasis, and worse overall survival in EC patients. Knockdown of TROAP inhibited the proliferation, migration, invasion, and glycolytic capacity of EC cells. E2F1 was identified as a transcriptional activator of TROAP. E2F1 over-expression enhanced TROAP expression and promoted EC cell proliferation, migration, and glycolysis in a TROAP-dependent manner. TROAP knockdown suppressed tumor growth in vivo. Conclusion. TROAP is transcriptionally activated by E2F1 and promotes EC progression by enhancing cell proliferation, metastasis, and glycolysis. The E2F1-TROAP axis may serve as a potential therapeutic target for EC treatment.
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    FOXO1 expression in villous trophoblast of preeclampsia and fetal growth restriction placentas
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Sheridan, Rachel; Belludi, Chethan; Khoury, Jane; Stanek, Jerzy; Handwerger, Stuart
    Oxidative stress and increased apoptosis are implicated in the pathogenesis of many disorders of pregnancy, including preeclampsia (PE) and fetal growth restriction (FGR). Since the transcription factor FOXO1 (forkhead box protein O1) is implicated in the regulation of a variety of cellular processes, including resistance to oxidative stress, apoptosis and morphogenesis of the placenta, we examined whether FOXO1 expression is abnormal in placentas from patients with PE or FGR. Paracentral sections from grossly unremarkable areas of 9 or 10 placentas each from early third trimester patients (31.7±5.0 weeks) with mild PE, severe PE, FGR and a gestational age-matched comparison group (GA controls) were double immunostained for FOXO1 and E-cadherin, the latter distinguishing villous cytotrophoblast cells (CTB) from syncytiotrophoblast (STB). The numbers of FOXO1-positive and FOXO1 negative STB and CTB nuclei were determined on ten 20x objective fields of each placenta section by three observers who were blinded to the clinical outcome. The results were evaluated by a generalized linear mixed model. In mild PE, FOXO1-positive STB nuclei were significantly decreased in number and FOXO1-negative STB nuclei were increased as compared to GA controls. However, the number of FOXO1-positive and FOXO1- negative CTB nuclei were not significantly changes as compared to GA controls. In severe PE and FGR, the numbers of FOXO-positive and FOXO1-negative STB and CTB were not statistically different from GA controls. Since FOXO1 is critical for placental cellular morphogenesis, abnormal FOXO1 expression may contribute in part to the abnormal trophoblast differentiation in mild PE. The differences in FOXO1 expression in mild and severe PE are consistent with other studies suggesting that the two forms of PE are different disease processes.