The crosstalk between ubiquitination and endocrine therapy

Ge, Yidong; Zhan, Ziqing; Ye, Meng; Jin, Xiaofeng

doi:10.1007/s00109-023-02300-z

Cited by 2 publications

(6 citation statements)

References 204 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fulvestrant is the only selective estrogen receptor degrader (SERD) approved by the Food and Drug Administration (FDA), which exhibits its antitumor effect through two mechanisms [ 2 ]. On the one hand, it competitively binds to ERα with estrogen, thereby inhibiting the activation of the ERα-mediated signaling pathways.…”

Section: Resultsmentioning

confidence: 99%

“…Endometrial cancer (EC) is one of the most common gynecological malignancies and the sixth most common malignant disease in the world [ 1 ]. At present, EC patients with progesterone receptor and/or estrogen receptor positive could be considered for endocrine therapy [ 2 ]. Progesterone is commonly used in the treatment of well-differentiated relapsed EC patients or patients with advanced EC requiring fertility preservation [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…At present, EC patients with progesterone receptor and/or estrogen receptor positive could be considered for endocrine therapy [ 2 ]. Progesterone is commonly used in the treatment of well-differentiated relapsed EC patients or patients with advanced EC requiring fertility preservation [ 2 ]. It prolong progression-free survival (PFS) but has no influence on overall survival (OS) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Progesterone is commonly used in the treatment of well-differentiated relapsed EC patients or patients with advanced EC requiring fertility preservation [ 2 ]. It prolong progression-free survival (PFS) but has no influence on overall survival (OS) [ 2 ]. Tamoxifen, a selective estrogen receptor modulator, competes with estrogen for estrogen receptor alpha (ERα), thereby inhibiting the development of EC [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Upon binding to estrogen, ERα forms dimers and translocated into the nucleus, where it summons co-activators or co-repressors to the estrogen response element (ERE) on the target gene promoter, thereby activating or inhibiting transcription [ 5 ]. Studies have shown that ERα protein is highly expressed in EC, and anti-ERα therapy has been shown to be effective in EC [ 2 ]. However, the mechanism of the abnormally high expression of ERα in EC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Endometrial cancer (EC) derived G3BP1 overexpression and mutant promote EC tumorigenesis and metastasis via SPOP/ERα axis

Ge,

Jin,

Chen

et al. 2023

Cell Commun Signal

Self Cite

View full text Add to dashboard Cite

Background Ras-GTPase-activating protein binding protein 1 (G3BP1) is an oncogenic factor, which highly expressed in a variety of cancers. In recent years, G3BP1 has been reported to promote the development of prostate cancer by inhibiting the degradation of AR through inhibiting SPOP. However, whether G3BP1 contributes in a similar manner to the abnormal accumulation of ERα, which is also an important target for hormone therapy, remains unknown. This article addresses this issue and explores potential mechanisms. Methods Bioinformatics tools were used for G3BP1 expression analysis, survival analysis, and clinical association analysis. Immunohistochemical staining was used to examine the correlation between G3BP1 and ERα in EC patients. In addition, western blot and co-immunoprecipitation were used to detect the half-life of G3BP1 and mutant, and the effect of G3BP1 and mutant on the ubiquitination and degradation of ERα mediated by SPOP. Then, the oncogenic functions of G3BP1 dependent on the SPOP/ERα axis were determined by CCK8 cell proliferation assay, colony formation assay and cell migration assay. Finally, we established the EC cells treated or untreated with fulvestrant, exploring the possibility of fulvestrant combined with the reduction of G3BP1 to improve the efficacy of fulvestrant. Results G3BP1 is abnormally high expressed and characterized by high-frequency mutation in EC. In addition, there is a positive correlation between G3BP1 protein and ERα protein. Mechanistically, both G3BP1 and mutant, the latter is displaying the longer half-life, competitively bind SPOP with ERα, thereby inhibiting SPOP-mediated ubiquitination and degradation of ERα. Functionally, G3BP1 and mutant promote the proliferation and migration of EC cells by regulating the G3BP1/SPOP/ERα axis. However, fulvestrant can reverse the cancer-promoting effects of G3BP1 and mutant. Conclusions G3BP1 and its mutant positively regulate ERα signaling pathway by inhibiting SPOP-mediated ubiquitination and degradation of ERα, indicating the promising effect of fulvestrant on the suppression the occurrence and development of EC with high expressed G3BP1 and G3BP1 mutants.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Endometrial cancer (EC) derived G3BP1 overexpression and mutant promote EC tumorigenesis and metastasis via SPOP/ERα axis

Ge,

Jin,

Chen

et al. 2023

Cell Commun Signal

Self Cite

View full text Add to dashboard Cite

show abstract

Crosstalk of methylation and tamoxifen in breast cancer (Review)

Shen,

He,

et al. 2024

Mol Med Rep

View full text Add to dashboard Cite

Tamoxifen is a widely used anti-estrogen drug in the endocrine therapy of breast cancer (BC). It blocks estrogen signaling by competitively binding to estrogen receptor α (ERα), thereby inhibiting the growth of BC cells. However, with the long-term application of tamoxifen, a subset of patients with BC have shown resistance to tamoxifen, which leads to low overall survival and progression-free survival. The molecular mechanism of resistance is mainly due to downregulation of ERα expression and abnormal activation of the PI3K/AKT/mTOR signaling pathway. Moreover, the downregulation of targeted gene expression mediated by DNA methylation is an important regulatory mode to control protein expression. In the present review, methylation and tamoxifen are briefly introduced, followed by a focus on the effect of methylation on tamoxifen resistance and sensitivity. Finally, the clinical application of methylation for tamoxifen is described, including its use as a prognostic indicator. Finally, it is hypothesized that when methylation is used in combination with tamoxifen, it could recover the resistance of tamoxifen.

show abstract

The crosstalk between ubiquitination and endocrine therapy

Cited by 2 publications

References 204 publications

Endometrial cancer (EC) derived G3BP1 overexpression and mutant promote EC tumorigenesis and metastasis via SPOP/ERα axis

Endometrial cancer (EC) derived G3BP1 overexpression and mutant promote EC tumorigenesis and metastasis via SPOP/ERα axis

Crosstalk of methylation and tamoxifen in breast cancer (Review)

Contact Info

Product

Resources

About