Potential therapeutic strategy for oral squamous cell carcinoma by ErbB3-binding protein 1 gene transfer

Zhou, Xiaoyan; Chen, Wantao; Zhang, Yuexing; Sun, Jian; Wang, Qing; Yu, Youcheng

doi:10.1007/s00432-009-0730-1

Cited by 7 publications

(9 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with these findings, down-regulation of PA2G4-p48 results in a reduction in malignant phenotypes including invasion and anchorage-independent growth (69). In contrast to these findings, ectopic expression of full-length PA2G4 cDNA in OSCC cell lines results in decreased growth and proliferation (71). Similar findings have been demonstrated in salivary adenoid cystic carcinoma (59).…”

Section: The Tumor Promoting Role Of Pa2g4-p48supporting

confidence: 63%

A structural view of PA2G4 isoforms with opposing functions in cancer

Stevenson

Gorman

Koach

et al. 2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

The role of Proliferation-Associated protein 2G4 (PA2G4), alternatively known as ErbB3-binding protein 1 (EBP1), in cancer has become apparent over the past 20 years. PA2G4 expression levels are correlated with prognosis in a range of human cancers including neuroblastoma, cervical, brain, breast, prostate, pancreatic, hepatocellular, and other tumors. There are two PA2G4 isoforms, PA2G4-p42 and PA2G4-p48, and although both isoforms of PA2G4 regulate cellular growth and differentiation, these isoforms often have opposing roles depending on the context. Therefore, PA2G4 can function either as a contextual tumor suppressor or as an oncogene depending on the tissue being studied. However, it is unclear how distinct structural features of the two PA2G4 isoforms translate into different functional outcomes. In this review, we examine published structures to identify important structural and functional components of PA2G4 and consider how they may explain its crucial role in the malignant phenotype. We will highlight the lysine-rich regions, protein-protein interaction sites and post-translational modifications of the two PA2G4 isoforms and relate these to the functional cellular role of PA2G4. These data will enable a better understanding of the function and structure relationship of the two PA2G4 isoforms and highlight the care that will need to be undertaken for those who wish to conduct isoform-specific structure-based drug design campaigns.

show abstract

Section: The Tumor Promoting Role Of Pa2g4-p48supporting

confidence: 63%

A structural view of PA2G4 isoforms with opposing functions in cancer

Stevenson

Gorman

Koach

et al. 2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Expression of Ebp1 at both the mRNA and protein levels is significantly decreased in prostate cancer tissue as compared with normal and benign prostate tissue (X. Zhou et al, 2010; H. . In the LNCaP human prostate cancer cell line, Ebp1 physically interacts with the AR and overexpression of Ebp1 inhibits AR target gene expression (Y.…”

Section: Prostate Cancermentioning

confidence: 99%

“…Ebp1 decreases AR protein levels by affecting AR promoter activity and also accelerate AR mRNA decay through its physical interaction with a conserved UC-rich motif within its 3′untranslated region (X. Zhou et al, 2010). Ebp1 also reduces the expression of both AR and its target genes at the protein level in castration-resistant prostate cancer (H. Zhou et al, 2011; Figure 2).…”

Section: Prostate Cancermentioning

confidence: 99%

“…Ebp1 harbors a LXXLL motif that mediates the interaction with nuclear hormone receptors (Heery, Kalkhoven, Hoare, & Parker, ; Y. Zhang et al, ). Expression of Ebp1 at both the mRNA and protein levels is significantly decreased in prostate cancer tissue as compared with normal and benign prostate tissue (X. Zhou et al, ; H. Zhou, Zhang, & Hamburger, ). In the LNCaP human prostate cancer cell line, Ebp1 physically interacts with the AR and overexpression of Ebp1 inhibits AR target gene expression (Y. Zhang et al, ), suggesting that Ebp1 may regulate prostate cancer progression through AR signaling.…”

Section: Controversial Functions Of Ebp1 Isoformsmentioning

confidence: 99%

See 1 more Smart Citation

The role of ErbB3 binding protein 1 in cancer: Friend or foe?

Nguyen

Hoang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

ErbB3, a member of the epidermal growth factor receptor family, reportedly plays an essential role in the regulation of cancer progression and therapeutic resistance. Numerous studies have indicated that ErbB3 binding protein 1 (Ebp1), a binding partner for ErbB3, plays an important regulatory role in the expression and function of ErbB3, but there is no agreement as to whether Ebp1 also has an ErbB3-independent function in cancer and how it might contribute to tumorigenesis. In this review, we will discuss the different functions of the two Ebp1 isoforms, p48 and p42, that may be responsible for the potentially dual role of Ebp1 in cancer growth.

show abstract

“…Following heregulin treatment, EBP1 translocates in the nucleus where it inhibits the transcription of E2F-regulated promoters, among which E2F1 transcription factor, D1 and E cyclins ( 14 ) and androgen receptor (AR) ( 15 ). Many studies have demonstrated the suppressor role of p48 in vivo , as it inhibits the growth and invasion of adenoid cystic carcinoma ( 16 ) and oral squamous cell carcinoma ( 17 ). The downregulation of the longer isoform of EBP1 is also associated with hormone resistance in prostate cancer tissues ( 12 ), while in human bladder cancer tissues ( 18 ) and hepatocellular carcinoma ( 19 ) the decreased expression was associated with advanced pathologic stage and poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

EBP1 protein modulates the expression of human MHC class II molecules in non-hematopoietic cancer cells

Pisapia

Barba

Cortese

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Many solid tumours including melanoma, glioblastoma, and breast carcinomas express MHC class II molecules (MHC II). The surface expression of these molecules confers to non-hematopoietic tumour cells the role of non-professional antigen presenting cells and the ability to potentially stimulate tumour-specific CD4+ T cell response. We studied EBP1, an ErbB3 binding protein, and the effects of p48 and p42 isoforms on the MHC II expression in U87 glioblastoma, M14 melanoma and MCF7 mammary carcinoma cell lines. We found that overexpression of p48 increases MHC II transcription in U87 and M14, through upregulation of CIITA transactivator and STAT1 phosphorylation. In addition, p48 protein influences MHC II expression by increasing mRNA stability. In melanoma and glioblastoma cell lines, p48 isoform functions as oncogene promoting tumour growth, while p42 isoform, that does not affect MHC II expression, acts as a tumour suppressor by blocking cell growth and inducing apoptosis. In contrast, p48 seems to act as tumour suppressor in breast carcinoma inhibiting proliferation, favouring apoptosis, and inducing a slight increase of MHC II expression similar to p42. Our data highlight the tissue specificity function of EBP1 isoforms and demonstrate that only the oncogene p48 activates MHC II expression in human solid tumours, via STAT1 phosphorylation, in order to affect tumour progression by triggering specific immune response.

show abstract

Potential therapeutic strategy for oral squamous cell carcinoma by ErbB3-binding protein 1 gene transfer

Abstract: Ectopic expression of Ebp1 mediates multiple antitumor activities against OSCC, suggesting a potential of Ebp1-based novel therapy for clinical OSCC treatment.

Cited by 7 publications

References 24 publications

A structural view of PA2G4 isoforms with opposing functions in cancer

A structural view of PA2G4 isoforms with opposing functions in cancer

The role of ErbB3 binding protein 1 in cancer: Friend or foe?

EBP1 protein modulates the expression of human MHC class II molecules in non-hematopoietic cancer cells

Contact Info

Product

Resources

About