FOXM1 promotes tumor cell invasion and correlates with poor prognosis in early-stage cervical cancer

He, Shanyang; Shen, Hongwei; Xu, Lin; Zhao, Xiaohui; Li, Yuan; Niu, Gang; Zhang, You; Yao, Shuzhong

doi:10.1016/j.ygyno.2012.08.036

Cited by 55 publications

(52 citation statements)

References 41 publications

(82 reference statements)

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“…In the present study, FOXM1 expression was significantly higher in cervical cancer tissues than in normal cervical tissues (squamous carcinoma vs. normal cervical tissue, P<0.001; adenocarcinoma vs. normal cervical tissue, P=0.014). This result is in accordance with the studies by Chan et al (20) and He et al (21). The present study also revealed that the expression of FOXM1 correlated with cancer invasion (P=0.011), similarly to the results reported by Chan et al (20) and He et al (21), who also noted an association between FOXM1 expression and tumor stage.…”

Section: A B C D E F G Hsupporting

confidence: 93%

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

et al. 2016

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Abstract. Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues. In addition, the association of these molecules with clinicopathological parameters, and the association between FOXM1 and various molecules involved in the Hh signaling pathway was investigated. The results indicated that FOXM1 and Hh signaling molecules were overexpressed in cervical cancer tissues. The protein expression levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO) correlated with the clinical stage of the tumors, while the protein expression levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the pathological grade of the tumors. The expression levels of GLI1 were lower in tissues without lymph node metastasis than in tissues with lymph node metastasis. In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in cancer tissues. These findings confirmed the participation of FOXM1 and the Hh signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be a downstream target gene of the Hh signaling pathway in cervical cancer provides a potential novel diagnostic and therapeutic target for cervical cancer.

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Section: A B C D E F G Hsupporting

confidence: 93%

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

et al. 2016

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“…10,11 Few studies have attempted to identify biomarkers to predict overall survival of squamous cell carcinoma patients, but the results are not satisfactory. 5–8,12–15 The aims of this study were to identify and validate other candidate biomarkers for HSIL and squamous cell carcinoma, including keratin 4 (KRT4) and keratin 17 (KRT17), and to evaluate KRT17 as a potential prognostic biomarker for patients with cervical squamous cell carcinoma.…”

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confidence: 99%

Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker

et al. 2014

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Most previously described immunohistochemical markers of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma may help to improve diagnostic accuracy but have a minimal prognostic value. The goals of the current study were to identify and validate novel candidate biomarkers that could potentially improve diagnostic and prognostic accuracy for cervical HSIL and squamous cell carcinoma. Microdissected tissue sections from formalin-fixed paraffin-embedded normal ectocervical squamous mucosa, low-grade squamous intraepithelial lesion (LSIL), HSIL and squamous cell carcinoma sections were analyzed by mass spectrometry-based shotgun proteomics for biomarker discovery. The diagnostic specificity of candidate biomarkers was subsequently evaluated by immunohistochemical analysis of tissue microarrays. Among 1750 proteins identified by proteomic analyses, keratin 4 (KRT4) and keratin 17 (KRT17) showed reciprocal patterns of expression in the spectrum of cases ranging from normal ectocervical squamous mucosa to squamous cell carcinoma. Immunohistochemical studies confirmed that KRT4 expression was significantly decreased in squamous cell carcinoma compared with the other diagnostic categories. By contrast, KRT17 expression was significantly increased in HSIL and squamous cell carcinoma compared with normal ectocervical squamous mucosa and LSIL. KRT17 was also highly expressed in immature squamous metaplasia and in endocervical reserve cells but was generally not detected in mature squamous metaplasia. Furthermore, high levels of KRT17 expression were significantly associated with poor survival of squamous cell carcinoma patients (Hazard ratio = 14.76, P = 0.01). In summary, both KRT4 and KRT17 expressions are related to the histopathology of the cervical squamous mucosa; KRT17 is highly overexpressed in immature squamous metaplasia, in HSIL, and in squamous cell carcinoma and the level of KRT17 in squamous cell carcinoma may help to identify patients who are at greatest risk for cervical cancer mortality.

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“…Bioinformatic analysis results indicated that FOXM1 may be a direct miR-197 target gene. FOXM1 was selected for further study for the following reasons: i) FOXM1 is a member of the forkhead superfamily of transcription factors and has been identified to be upregulated in a number of types of human cancer including lung, breast, liver, pancreatic and cervical cancer, as well as in glioblastoma (28)(29)(30); and ii) functional studies have revealed FOXM1 to be involved in numerous biological processes including cell proliferation, cell cycle progression, cell differentiation, DNA damage repair, tissue homeostasis, angiogenesis and apoptosis (31).…”

Section: Discussionmentioning

confidence: 99%

miR‑197 is downregulated in cervical carcinogenesis and suppresses cell proliferation and invasion through targeting forkhead box M1

Mao

et al. 2018

Oncol Lett

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Abstract. Cervical cancer is the second most common type of cancer in females worldwide. It has been demonstrated that microRNAs (miRs) serve important roles in the occurrence and development of various types of cancer, including cervical cancer. The results of the present study revealed that miR-197 was downregulated in cervical cancer tissues and cell lines. Restoration of miR-197 expression significantly inhibited cell viability and invasion of cervical cancer. Additionally, forkhead box M1 (FOXM1) was identified as a direct target gene of miR-197. Bioinformatic analysis revealed that FOXM1 was a potential target gene of miR-197. Luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that miR-197 decreased FOXM1 expression through direct binding to its 3'-untranslated region. Furthermore, the effects of FOXM1 underexpression were comparable with the effects induced by miR-197 overexpression in cervical cancer cells, suggesting that FOXM1 acted as a downstream effector in miR-197-mediated proliferation and invasion of cervical cancer cells. The results of the present study suggested that miR-197 inhibited growth and metastasis of cervical cancer by directly targeting FOXM1.

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FOXM1 promotes tumor cell invasion and correlates with poor prognosis in early-stage cervical cancer

Cited by 55 publications

References 41 publications

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker

miR‑197 is downregulated in cervical carcinogenesis and suppresses cell proliferation and invasion through targeting forkhead box M1

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