Therapy-induced senescence promotes breast cancer cells plasticity by inducing Lipocalin-2 expression

Morales-Valencia, Jorge; Lau, Lena; Martí-Nin, Teresa; Özerdem, Uğur; Gourichon, David

doi:10.1038/s41388-022-02433-4

Cited by 21 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The novel action of RGS10 in EMT in breast cancer appears to be dependent on LNC2, also known as neutrophil gelatinase-associated lipocalin, siderocalin, uterocalin, and oncogene -Valencia et al, 2022;Yang et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

Liu,

Jiang,

Qiu

et al. 2024

Preprint

View full text Add to dashboard Cite

Distant metastasis is the major cause of death in patients with breast cancer. Epithelial–mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulate metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and miR-539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

Liu,

Jiang,

Qiu

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Senescence and the associated SASP can affect cells within the tumor microenvironment (TME). The SASP was shown to promote tumorigenesis [ 66 ], EMT [ 67 , 68 , 69 ], cancer stemness [ 70 , 71 ], anticancer drug resistance [ 72 , 73 , 74 ], angiogenesis [ 75 , 76 , 77 , 78 ], immune suppression to promote tumorigenesis [ 79 , 80 ], and tumor suppression by the immune clearance of senescent cells [ 81 ]. Figure 4 shows the roles of the SASP, including tumor suppression and tumor promotion.…”

Section: Roles Of Sasp In Cancer Cell Proliferation and Therapeutic R...mentioning

confidence: 99%

Section: Roles Of Sasp In Cancer Cell Proliferation and Therapeutic R...mentioning

confidence: 99%

“…The SASP increased the expression of lipocalin-2 (LCN2) to enhance breast cancer cell proliferation and migration [ 66 ]. High levels of LCN2 could predict the poor prognosis of patients with breast cancer [ 66 ]. The inactivation of LCN2 enhanced the response to chemotherapeutic drugs in mouse models of breast cancer [ 64 ].…”

Section: Roles Of Sasp In Cancer Cell Proliferation and Therapeutic R...mentioning

confidence: 99%

See 1 more Smart Citation

The Potential of Senescence as a Target for Developing Anticancer Therapy

Shim

Jeoung

2023

IJMS

View full text Add to dashboard Cite

Senescence occurs in response to various stimuli. Senescence has attracted attention because of its potential use in anticancer therapy as it plays a tumor-suppressive role. It also promotes tumorigeneses and therapeutic resistance. Since senescence can induce therapeutic resistance, targeting senescence may help to overcome therapeutic resistance. This review provides the mechanisms of senescence induction and the roles of the senescence-associated secretory phenotype (SASP) in various life processes, including therapeutic resistance and tumorigenesis. The SASP exerts pro-tumorigenic or antitumorigenic effects in a context-dependent manner. This review also discusses the roles of autophagy, histone deacetylases (HDACs), and microRNAs in senescence. Many reports have suggested that targeting HDACs or miRNAs could induce senescence, which, in turn, could enhance the effects of current anticancer drugs. This review presents the view that senescence induction is a powerful method of inhibiting cancer cell proliferation.

show abstract

“…[11] Breast cancer cells exposed to the senescence-associated secretory phenotype also strongly upregulates the lipocalin-2, which was critical for the increased migration in BRCA cells. [12] Regarding the tumor microenvironment, the secreted IL-6 during senescence also recruits the myeloid suppressive cells to inhibit T-cells function. [13] It follows that senescence plays an important role as a double-edged sword in cancer development.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a 6-signature risk model associated with cellular senescence for predicting the prognosis of breast cancer

Zhang,

Yu,

Zhu

et al. 2023

Medicine

View full text Add to dashboard Cite

This study focused on screening novel markers associated with cellular senescence for predicting the prognosis of breast cancer. The RNA-seq expression profile of BRCA and clinical data were obtained from TCGA. The pam algorithm was used to cluster patients based on senescence-related genes. The weighted gene co-expression network analysis was used to identify co-expressed genes, and LASSO-Cox analysis was performed to build a risk prognosis model. The performance of the model was also evaluated. We additionally explored the role of senescence in cancer development and possible regulatory mechanism. The patients were clustered into 2 subtypes. A total of 5259 genes significantly related to senescence were identified by weighted gene co-expression network analysis. LASSO-Cox finally established a 6-signature risk model (ADAMTS8, DCAF12L2, PCDHA10, PGK1, SLC16A2, and TMEM233) that exhibited favorable and stable performance in our training, validation, and whole BRCA datasets. Furthermore, the superiority of our model was also observed after comparing it to other published models. The 6-signature was proved to be an independent risk factor for prognosis. In addition, mechanism prediction implied the activation of glycometabolism processes such as glycolysis and TCA cycle under the condition of senescence. Glycometabolism pathways were further found to negatively correlate with the infiltration level of CD8 T-cells and natural killer cells but positively correlate with M2 macrophage infiltration and expressions of tissue degeneration biomarkers, which suggested the deficit immune surveillance and risk of tumor migration. The constructed 6-gene model based on cellular senescence could be an effective indicator for predicting the prognosis of BRCA.

show abstract

Therapy-induced senescence promotes breast cancer cells plasticity by inducing Lipocalin-2 expression

Abstract: Uncropped gels.Lanes used for the figures presented in the manuscript are indicated with stars () above them. Full unedited gel for Figure 2E. Tubulin * * * * * LCN2 * * Full unedited gels for Figure 2H.

Cited by 21 publications

References 46 publications

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

The Potential of Senescence as a Target for Developing Anticancer Therapy

Establishment of a 6-signature risk model associated with cellular senescence for predicting the prognosis of breast cancer

Contact Info

Product

Resources

About

Therapy-induced senescence promotes breast cancer cells plasticity by inducing Lipocalin-2 expression

Abstract: Uncropped gels.Lanes used for the figures presented in the manuscript are indicated with stars (*) above them. Full unedited gel for Figure 2E. Tubulin * * * * * * LCN2 * * Full unedited gels for Figure 2H.

Cited by 21 publications

References 46 publications

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

The Potential of Senescence as a Target for Developing Anticancer Therapy

Establishment of a 6-signature risk model associated with cellular senescence for predicting the prognosis of breast cancer

Contact Info

Product

Resources

About

Abstract: Uncropped gels.Lanes used for the figures presented in the manuscript are indicated with stars () above them. Full unedited gel for Figure 2E. Tubulin * * * * * LCN2 * * Full unedited gels for Figure 2H.