Overexpression of Her-2 upregulates FoxM1 in gastric cancer

Qi, Weiwei; Li, Xiaoxiao; Zhang, Yongchun; Yao, Ruyong; Qiu, Wensheng; Tang, Dongfang; Liang, Jun

doi:10.3892/ijmm.2014.1732

Cited by 6 publications

(3 citation statements)

References 35 publications

(48 reference statements)

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“…Moreover, we found that the Hh-Gli1 signaling pathway regulated the expression of FoxM1 in CRC cells and that the inhibition of FoxM1 impeded Gli1-mediated CRC cell proliferation. FoxM1 expression was also recently reported to be modulated by many other transcription factors, and Her2 reportedly upregulated FoxM1 expression in gastric cancer [ 51 ]. FoxM1 was also shown to be transactivated by HSF1, which promoted the survival of glioma cells under heat shock stress [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

Wang

et al. 2017

J Exp Clin Cancer Res

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BackgroundRecent evidence suggests that the aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas, including colorectal cancer (CRC). Forkhead box M1 (FoxM1) controls the expression of a number of cell cycle regulatory proteins, and FoxM1 expression is elevated in a broad range of human malignancies, which suggests that it plays a crucial role in tumorigenesis. However, the mechanisms underlying FoxM1 expression are not fully understood. Here, we aim to further investigate the molecular mechanism by which Gli1 regulates FoxM1 in CRC.MethodsWestern blotting and immunohistochemistry (IHC) were used to evaluate FoxM1 and Gli1 protein expression, respectively, in CRC tissues and matched adjacent normal mucosa. BrdU (5-bromo-2′-deoxyuridine) and clone formation assays were used to clarify the influence of FoxM1 on CRC cell growth and proliferation. Chromatin immunoprecipitation (ChIP) and luciferase experiments were performed to explore the potential mechanisms by which Gli1 regulates FoxM1. Additionally, the protein and mRNA expression levels of Gli1 and FoxM1 in six CRC cell lines were measured using Western blotting and real-time PCR. Finally, the effect of Hh signaling on the expression of FoxM1 was studied in cell biology experiments, and the effects of Hh signaling activation and FoxM1 inhibition on the distribution of CRC cells among cell cycle phases was assessed by flow cytometry.ResultsGli1 and FoxM1 were abnormally elevated in human CRC tissues compared with matched adjacent normal mucosa samples, and FoxM1 is a downstream target gene of the transcription factor Gli1 in CRC and promoted CRC cell growth and proliferation. Moreover, the aberrant activation of Hh signaling promoted CRC cell proliferation by directly binding to the promoter of FoxM1 and transactivating the activity of FoxM1 in CRC cells.ConclusionThe dysregulation of the Hh-Gli1-FoxM1 axis is essential for the proliferation and growth of human CRC cells and offers a potent target for therapeutic intervention in CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0491-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

Wang

et al. 2017

J Exp Clin Cancer Res

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“…Since the association between HER-2 gene amplification and disease prognosis was demonstrated (10,11), overexpression of the gene has been observed in a variety of primary human carcinoma, including breast cancer (12,13), gastric cancer (14,15), gastroesophageal adenocarcinomas (16) and mucinous epithelial ovarian cancer (17). Initially, HER-2 was found to be upregulated in meningioma (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Role of HER-2 activity in the regulation of malignant meningioma cell proliferation and motility

Wang

et al. 2015

Molecular Medicine Reports

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Meningiomas are common types of intracranial tumor. Invasive and malignant meningiomas present a significant therapeutic challenge due to high rates of recurrence and invasion. Understanding the molecular mechanism of invasion may assist in designing novel therapeutic approaches and improving patient survival rates. The HER‑2 gene has been demonstrated to be a useful predictor of tumor aggression, which promotes the survival and growth of cancer cells through the mitogen‑activated protein kinase and/or phosphatidylinositol 3‑kinase (PI3K)/AKT pathway. Until now, few studies have investigated the associateion between meningiomas and the expression of HER‑2, and the significance of HER‑2 in meningiomas remains to be elucidated. The present study aimed to investigate the effects of the HER‑2 gene on the biological behaviors of human malignant meningioma cells. The results demonstrated that downregulation of the expression of HER‑2 by small interfering RNA in human meningioma cells significantly inhibited cell motility and proliferation, led to cell cycle arrest at the G0/G1‑phase and increased early apoptosis. By contrast, the overexpression of HER‑2 group resulted in meningioma cell invasion, migration and proliferation being significantly enhanced, cell cycle was promoted at the G1/S‑phase and early apoptosis was decreased. Accordingly, the inhibition of HER‑2 also prevented the protein expression of PI3K and phosphorylated AKT. The results demonstrated that regulation of the HER‑2 gene can affect the proliferation, apoptosis, invasion and metastasis abilities of human meningioma cells in vitro. Furthermore, PI3K/AKT may contribute to the carcinogenesis and development of human meningiomas in combination with HER-2.

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“…The FOXM1 regulon also showed great overlap with Kang doxorubicin resistance gene set. Recently, Qi W. et al demonstrated that the regulation of the level of ERBB2 in the gastric cancer cell lines, accordingly produced a change in the expression of FOXM1, indicating that the expression level of FOXM1 was at least partially regulated by ERBB2 [56]. Interestingly, Qi W. et al also revealed that FOXM1 and ERBB2 expression was associated with poor survival.…”

Section: Discussionmentioning

confidence: 99%

Gene Regulatory Network Characterization of Gastric Cancer’s Histological Subtypes: Distinctive Biological and Clinically Relevant Master Regulators

Russi

Marano

Laurino

et al. 2022

Cancers

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Gastric cancer (GC) molecular heterogeneity represents a major determinant for clinical outcomes, and although new molecular classifications have been introduced, they are not easy to translate from bench to bedside. We explored the data from GC public databases by performing differential gene expression analysis (DEGs) and gene network reconstruction to identify master regulators (MRs), as well as a gene set analysis (GSA) to reveal their biological features. Moreover, we evaluated the association of MRs with clinicopathological parameters. According to the GSA, the Diffuse group was characterized by an epithelial-mesenchymal transition (EMT) and inflammatory response, while the Intestinal group was associated with a cell cycle and drug resistance pathways. In particular, the regulons of Diffuse MRs, such as Vgll3 and Ciita, overlapped with the EMT and interferon-gamma response, while the regulons Top2a and Foxm1 were shared with the cell cycle pathways in the Intestinal group. We also found a strict association between MR activity and several clinicopathological features, such as survival. Our approach led to the identification of genes and pathways differentially regulated in the Intestinal and Diffuse GC histotypes, highlighting biologically interesting MRs and subnetworks associated with clinical features and prognosis, suggesting putative actionable candidates.

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Overexpression of Her-2 upregulates FoxM1 in gastric cancer

Cited by 6 publications

References 35 publications

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

Role of HER-2 activity in the regulation of malignant meningioma cell proliferation and motility

Gene Regulatory Network Characterization of Gastric Cancer’s Histological Subtypes: Distinctive Biological and Clinically Relevant Master Regulators

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