Ubiquitin-specific protease 4 inhibits breast cancer cell growth through the upregulation of PDCD4

Li, Yang; Jiang, Daqing; Zhang, Qi; Liu, Xiaoli; Cai, Zhengang

doi:10.3892/ijmm.2016.2685

Cited by 42 publications

(39 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…a and b ). In contrast, a recent study suggested that USP4 also exhibits an oncosuppressive property by targeting programmed cell death 4 (PCD4), consistent with the results obtained in some other cancer types . Thus, these results, together with our observation, imply a divergent role of USP4 in breast cancer progression.…”

Section: Discussionsupporting

confidence: 91%

A PAK5–DNPEP–USP4 axis dictates breast cancer growth and metastasis

Geng

Zhang

et al. 2019

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Although clinically associated with the progression of multiple cancers, the biological function of p21‐activated kinase 5 (PAK5) in breast cancer remains largely unknown. Here, we reveal that the PAK5–aspartyl aminopeptidase (DNPEP)–ubiquitin‐specific protease 4 (USP4) axis is involved in breast cancer progression. We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. Functionally, we demonstrate that DNPEP overexpression suppresses breast cancer cell proliferation and invasion and restricts breast cancer growth and metastasis in mice. Furthermore, we identify USP4 as a downstream target of the PAK5–DNPEP pathway; DNPEP mediates USP4 downregulation. Importantly, we verify that DNPEP expression is frequently downregulated in breast cancer tissues and is negatively correlated with PAK5 and USP4 expression. PAK5 decreases DNPEP abundance via the ubiquitin–proteasome pathway. Consistently, analyses of clinical breast cancer specimens revealed significantly increased PAK5 and USP4 levels and an association between higher PAK5 and USP4 expression and worse breast cancer patient survival. These findings suggest a pivotal role for PAK5‐elicited signaling in breast cancer progression.

show abstract

Section: Discussionsupporting

confidence: 91%

A PAK5–DNPEP–USP4 axis dictates breast cancer growth and metastasis

Geng

Zhang

et al. 2019

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…These studies demonstrate USP4 as a powerful tumour promoter and an important determinant for canonical oncogenic signalling. However, in breast cancer, USP4 was also recognized as a tumour suppressor for its up‐regulatory effect on programmed cell death 4 (PDCD4) to restrain tumour growth 20. Moreover, USP4 was able to target TRAF2 and TRAF6 for deubiquitination and thereafter inhibited TNFα‐induced cancer cell migration 34.…”

Section: Discussionmentioning

confidence: 99%

“…On the one hand, the elevated USP4 expression contributed to the growth of colorectal cancer via deubiquitination and stabilization of oncogene PRL‐3 19. On the other hand, USP4 could also exert its tumour‐suppressive role through inhibiting cell proliferation or promoting cell apoptosis in breast cancer and neck squamous cell carcinoma 20, 21. These results suggested that the impact of USP4 on cancer biology is tumour‐type specific and tissue‐context dependent.…”

Section: Introductionmentioning

confidence: 96%

Up‐regulated deubiquitinase USP4 plays an oncogenic role in melanoma

Guo

Pei

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin‐specific peptidase (USP) families are greatly implicated in modulating cancer biology. Herein, we first found that the expression of the deubiquitinase USP4 was significantly up‐regulated in melanoma tissues and cell lines. Furthermore, although USP4 knockdown had little impact on melanoma cell proliferation, it could increase the sensitivity to DNA damage agent cisplatin. We subsequently showed that USP4 regulated cisplatin‐induced cell apoptosis via p53 signalling. More importantly, USP4 could accentuate the invasive and migratory capacity of melanoma cells by promoting epithelial‐mesenchymal transition. Altogether, our results demonstrate that the up‐regulated USP4 plays an oncogenic role in melanoma by simultaneously suppressing stress‐induced cell apoptosis and facilitating tumour metastasis.

show abstract

“…Moreover, SRSF3 was also reported to modulate the expression of PDCD4 gene through the alternative splicing and translational mechanisms [111]. PDCD4 reportedly acted the tumor suppressor in repressing the transformation and immortality of cancer cells [113]. SRSF3 silencing was noted to reduce the relative level of PDCD4 isoform 2, containing the partial PDCD4 intron 3 in distinct cancer cells.…”

Section: Impacts Of Alternative Splicing Events On Apoptosismentioning

confidence: 99%

Differential Impacts of Alternative Splicing Networks on Apoptosis

Lin

Tsao

Lin

2016

IJMS

View full text Add to dashboard Cite

Apoptosis functions as a common mechanism to eliminate unnecessary or damaged cells during cell renewal and tissue development in multicellular organisms. More than 200 proteins constitute complex networks involved in apoptotic regulation. Imbalanced expressions of apoptosis-related factors frequently lead to malignant diseases. The biological functions of several apoptotic factors are manipulated through alternative splicing mechanisms which expand gene diversity by generating discrete variants from one messenger RNA precursor. It is widely observed that alternatively-spliced variants encoded from apoptosis-related genes exhibit differential effects on apoptotic regulation. Alternative splicing events are meticulously regulated by the interplay between trans-splicing factors and cis-responsive elements surrounding the regulated exons. The major focus of this review is to highlight recent studies that illustrate the influences of alternative splicing networks on apoptotic regulation which participates in diverse cellular processes and diseases.

show abstract

Ubiquitin-specific protease 4 inhibits breast cancer cell growth through the upregulation of PDCD4

Cited by 42 publications

References 32 publications

A PAK5–DNPEP–USP4 axis dictates breast cancer growth and metastasis

A PAK5–DNPEP–USP4 axis dictates breast cancer growth and metastasis

Up‐regulated deubiquitinase USP4 plays an oncogenic role in melanoma

Differential Impacts of Alternative Splicing Networks on Apoptosis

Contact Info

Product

Resources

About