Significance of Ebp1 and p53 protein expression in cervical cancer

Liu, Lei; Xd, Li; Hy, Chen; Js, Cui; Dy, Xu

doi:10.4238/2015.october.2.19

Cited by 14 publications

(15 citation statements)

References 14 publications

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“…EBP1 was originally identified as an ErbB3 binding protein which was considered as an oncogene or tumor suppressor in different circumstances (38–41) and has prognostic significance in a panel of cancers such as cervical (7, 42), pancreatic (6), hepatocellular (43), brain (44) and other tumors. Recent study has clarified that EBP1 possesses two isoforms, the longer form P48 and the shorter form P42, which distinctively regulate cell survival and differentiation (5).…”

Section: Discussionmentioning

confidence: 99%

“…The predominant P48 isoform can promote cell proliferation, differentiation or survival including cancer cells (4, 6), and localizes to both cytoplasm and nucleus (5). Moreover, correlation of high expression level of P48 with poor clinical outcomes in pancreatic ductal adenocarcinoma (6), brain tumor (4), cervical (7) and prostate cancer patients (8) suggests P48 is closely related with cancer progression. In contrast, the P42 isoform which lacks the N-terminal 54 amino acids is considered to be a potent tumor suppressor because of its growth inhibitory function (3, 5, 9).…”

Section: Introductionmentioning

confidence: 99%

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Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer

et al. 2017

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The ErbB3 receptor binding protein EBP1 encodes two alternatively spliced isoforms p48 and p42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 p48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 p48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function. In contrast, EBP1 p42 bound to both the F-box domain of FBXW7 as well as FBXW7 substrates. This adapter function of EBP1 p42 stabilized the interaction of FBXW7 with its substrates and promoted FBXW7-mediated degradation of oncogenic targets, enhancing its overall tumor suppressing function. Overall, our results establish distinct physical and functional interactions between FBXW7 and EBP1 isoforms which yield their mechanistically unique isoform-specific functions of EBP1 in cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer

et al. 2017

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“…The level of p53 was also associated with lymph node metastasis (p < 0.05) [32]. A study in 60 cervical cancer samples and 60 controls also showed higher p53 levels in the cervical cancer samples than the normal samples (p < 0.05), and the elevated p53 level was also associated with lymph node metastasis (p < 0.05) [33]. This identifies p53 as a robust prognostic biomarker in cervical cancer, even though its regulatory mechanism needs to be elucidated further.…”

Section: Expression Profiles Of Biomarkersmentioning

confidence: 94%

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Cardoso

Castelletti

Lima-Filho

et al. 2017

Mutation Research/Reviews in Mutation Research

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Cervical cancer is primarily caused by Human papillomavirus (HPV) infection, but other factors such as smoking habits, co-infections and genetic background, can also contribute to its development. Although this cancer is avoidable, it is the fourth most frequent type of cancer in females worldwide and can only be treated with chemotherapy and radical surgery. There is a need for biomarkers that will enable early diagnosis and targeted therapy for this type of cancer. Therefore, a systems biology pipeline was applied in order to identify potential biomarkers for cervical cancer, which show significant reports in three molecular aspects: DNA sequence variants, DNA methylation pattern and alterations in mRNA/protein expression levels. CDH1, CDKN2A, RB1 and TP53 genes were selected as putative biomarkers, being involved in metastasis, cell cycle regulation and tumour suppression. Other ten genes (CDH13, FHIT, PTEN, MLH1, TP73, CDKN1A, CACNA2D2, TERT, WIF1, APC) seemed to play a role in cervical cancer, but the lack of studies prevented their inclusion as possible biomarkers. Our results highlight the importance of these genes. However, further studies should be performed to elucidate the impact of DNA sequence variants and/or epigenetic deregulation and altered expression of these genes in cervical carcinogenesis and their potential as biomarkers for cervical cancer diagnosis and prognosis.

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“…P53 protein expression in cervical cancer tissue samples was not correlated with patient age, grade and stage of tumors (p > 0.05). An earlier report on cervical cancer stated that the protein expression level of p53 in the tumor tissues was significantly higher compared to that of the normal adjacent tissue [35]. Moreover, the same study reported that p53 protein expression in cervical cancer tissue samples was not correlated with the patient age, tumor size, or family history [35].…”

Section: Discussionmentioning

confidence: 94%

Clinicopathologic Aspects of Squamous Cell Carcinoma of the Uterine Cervix: Role of PTEN, BCL2 and P53

et al. 2018

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Background: Squamous cell carcinoma (SCC) of the uterine cervix is a leading cause of morbidity and mortality among women. The alterations of Phosphatase and tensin homolog (PTEN), B-cell lymphoma 2 (Bcl2) and p53 expression seem to be significant in the development of various types of cancers. The altered expressions of PTEN, Bcl2 and p53 and their involvement in cancer of the uterine cervix are not well recognized. Aim: This study aimed at examining the expression patterns of PTEN, Bcl2 and p53 proteins and comparing them with the grade and stage of cervical cancer. Materials and Methods: Tissue blocks of SCC and ten cases of inflammatory lesions of the uterine cervix were examined immunohistochemically for the expression of PTEN, Bcl2 and p53 proteins. Results: Loss of PTEN expression was identified in 45.33% of cervical SCC and no expression was found in inflammatory lesions (p ≤ 0.05). PTEN expression was significantly associated with the clinical stage of SCC (61.36% and 45.16% in stages I–II and III–IV, respectively) (p < 0.05), but not with the degree of differentiation of the SCC. The expression of Bcl2 was significantly high (60%) in cancer cases than in control cases (p < 0.05). Bcl2 did not show any significant association with the histologic type and clinical stage of the SCC of the uterine cervix. The expression of p53 protein was significantly high (57.33%)) in cancer tissue, and no expression was noted in control cases (p < 0.05). Moreover, the expression pattern of p53 protein in cervical cancer tissue samples was not linked with the patient age, grade and stage of the cervical SCC (p > 0.05). Conclusion: The reduced expression of PETN and overexpressions of Bcl2 and p53 might play an indispensable role in carcinogenesis of cervical SCC. Moreover, a relationship was detected between PTEN expression and clinical stage of the cervical SCC.

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Significance of Ebp1 and p53 protein expression in cervical cancer

Cited by 14 publications

References 14 publications

Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer

Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Clinicopathologic Aspects of Squamous Cell Carcinoma of the Uterine Cervix: Role of PTEN, BCL2 and P53

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