WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer

Chen, Shuai; Wang, Han; Huang, Yufan; Li, Mingli; Cheng, Jianghong; Hu, Peng; Lu, Chuanhui; Zhang, Ya; Liu, Na; Zhang, Zhiming

doi:10.1186/s12943-017-0693-9

Cited by 29 publications

(24 citation statements)

References 100 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genome-wide association studies of cerebral white matter lesions indicate that WBP2 gene is high risk for leukoaraiosis, suggesting that WBP2 might be a key regulator of nervous system inflammation 16 . The relationship between inflammation and cancer is established and studies show that WBP2 expression can enhance the proliferation and metastatic ability of breast cancer cells 17 , 18 ; however, to our knowledge, the expression and function of WBP2 in glioma has not been reported.…”

Section: Introductionmentioning

confidence: 92%

WW domain-binding protein 2 acts as an oncogene by modulating the activity of the glycolytic enzyme ENO1 in glioma

et al. 2018

Self Cite

View full text Add to dashboard Cite

WW domain-binding protein 2 (WBP2) has been demonstrated as oncogenic in breast cancer. Many studies have revealed the WBP2 gene as a high-risk gene for leukoariaosis and cerebral white matter lesions is important in the pathologic stage of glioma development. This study aimed to illustrate the underlying mechanism by which WBP2 regulates the process of glioma development. The expression pattern of WBP2 in several tumor cells was determined, clarifying the carcinogenic action of WBP2 in glioma cells. Overexpression of WBP2 in glioma cells promoted cell proliferation and migration, and the number of S-phase cells, whereas the depletion of WBP2 by RNAi-mediated knockdown restrained cell growth and cell cycle progression. Upregulation of WBP2 significantly enhanced the tumorigenic ability of U251 cells in vivo. MS/GST pulldown assay identified α-enolase (ENO1) and Homer protein homolog 3 (Homer3) as novel potent interaction partners of WBP2. Knockdown of ENO1 or Homer3 allowed cell growth and migration to return to normal levels. Furthermore, in vitro and in vivo experiments indicated that the oncogenic role of WBP2 in glioma was through modulating ENO1 and glycolysis activity via the ENO1-PI3K/Akt signaling pathway. Collectively, these results reveal that WBP2 plays a vital role in the occurrence and development of glioma, indicating a target gene for glioblastoma treatment.

show abstract

Section: Introductionmentioning

confidence: 92%

WW domain-binding protein 2 acts as an oncogene by modulating the activity of the glycolytic enzyme ENO1 in glioma

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…WW domain-binding protein 2 (WBP2) interacts with WW domains, which regulate protein-protein interactions containing proline rich motifs [5]. WW domain-containing proteins such as Yes-associated protein (YAP) in the Hippo pathway, play significant roles in human malignancies related to dysregulation of cell survival and proliferation, such as lung, breast, gastric and liver cancers [6].…”

Section: Introductionmentioning

confidence: 99%

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

Song¹,

Wu²,

Xie³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Dysregulated expression of WW domain-binding protein 2 (WBP2) is associated with poor prognosis in ER+ breast cancer patients. However, its role in triple negative breast cancer (TNBC) has not been previously assessed. Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells. Methods: qRT-PCR, western blotting, and immunohistochemical staining were used to evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA-MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR-613 mimics, or miR-613 inhibitors were subject to assays for cell viability, apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting or qRT-PCR were employed to monitor changes in signaling pathway-related genes and proteins. Luciferase assays were performed to assess whether WBP2 is a direct target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo using mouse xenograft models. Results: The expression of WBP2 was upregulated in TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67 in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to the 3’-untranslated region (3’-UTR) of WBP2 and regulated the expression of WBP2. Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613. Conclusion: WBP2 overexpression is associated with the poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt signaling pathway.

show abstract

“…It contains an N-terminal pleckstrin homology-glucosyltransferase (GRAM) domain and three C-terminal PPxY motifs, which interact with multiple WW domain-containing proteins (Chen and Sudol, 1995). A previous study showed that Wbp2 functions as a coactivator for estrogen receptor and is closely linked to the development of breast cancer (Chen et al, 2017). The original method described by Huibregtse and colleagues relies on Rsp5-mediated ubiquitination of a truncated Wbp2 (Kim and Huibregtse, 2009).…”

Section: Resultsmentioning

confidence: 99%

Epidithiodiketopiperazines Inhibit Protein Degradation by Targeting Proteasome Deubiquitinase Rpn11

Zhang

Santos

et al. 2018

Cell Chemical Biology

View full text Add to dashboard Cite

The 26S proteasome is the major proteolytic machine for breaking down cytosolic and nuclear proteins in eukaryotes. Due to the lack of a suitable assay, it is difficult to measure routinely and quantitatively the breakdown of proteins by the 26S proteasome in vitro. In the present study, we developed an assay to monitor proteasome-mediated protein degradation. Using this assay, we discovered that epidithiodiketopiperazine (ETPs) blocked the degradation of our model substrate in vitro. Further characterization revealed that ETPs inhibited proteasome function by targeting the essential proteasomal deubiquitinase Rpn11 (POH1/PSMD14). ETPs also inhibited other JAMM (JAB1/MPN/Mov34 metalloenzyme) proteases such as Csn5 and AMSH. An improved ETP with fewer non-specific effects, SOP11, stabilized a subset of proteasome substrates in cells, induced the unfolded protein response, and led to cell death. SOP11 represents a class of Rpn11 inhibitor and provides an alternative route to develop proteasome inhibitors.

show abstract

WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer

Cited by 29 publications

References 100 publications

WW domain-binding protein 2 acts as an oncogene by modulating the activity of the glycolytic enzyme ENO1 in glioma

WW domain-binding protein 2 acts as an oncogene by modulating the activity of the glycolytic enzyme ENO1 in glioma

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

Epidithiodiketopiperazines Inhibit Protein Degradation by Targeting Proteasome Deubiquitinase Rpn11

Contact Info

Product

Resources

About