A look into the link between centrosome amplification and breast cancer

Zhang, Yingzi; Tian, Jiao; Qu, Chi; Peng, Yang; Lei, Jinwei; Sun, Lu; Zong, Beige; Liu, Shengchun

doi:10.1016/j.biopha.2020.110924

Cited by 15 publications

(17 citation statements)

References 175 publications

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“…3B, D; S3D). This early upregulation of centriole duplication genes is supported by the fact that CA was previously found in pre-cancerous and preinvasive breast carcinomas Pannu et al, 2015a;Guo et al, 2007;Zhang et al, 2020). Interestingly, the expression of genes which are required for CC was only upregulated in the most aggressive stages of breast cancer progression, particularly IDC (Fig.…”

Section: Expression Levels Of Centrosome Duplication and Clustering G...supporting

confidence: 68%

“…Our results led us to hypothesize that the loss of epithelial properties might facilitate the clustering of extra-centrosomes in cancer cells. CA is often observed in breast cancer and underlies tumor aggressiveness and prognostic of worse outcomes (Denu et al , 2016; Singh et al , 2020; Lingle et al , 2002; Salisbury; Zhang et al , 2020; D’Assoro et al , 2002; Pannu et al , 2015a; Marteil et al , 2018). Metastasis of breast cancer cells requires decreased cell–cell adhesion and cells to undergo the EMT, in which epithelial cells acquire a motile mesenchymal phenotype (Roche, 2018).…”

Section: Resultsmentioning

confidence: 99%

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High prevalence and dependence of centrosome clustering in mesenchymal tumors and leukemia

Marín

Marteil

Fresmann

et al. 2023

Preprint

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The presence of supernumerary centrosomes is a hallmark of cancer and is frequently observed in aggressive tumors. Cancer cells with centrosome amplification achieve pseudo-bipolar spindles through specific coping mechanisms in order to survive. However, their distribution and prevalence in cancer remain largely unknown. Here, using the NCI60 panel of cancer cell lines, we show that the presence of coping strategies correlates with centrosome amplification, with the clustering of extra-centrosomes within the two spindle poles being the most widespread mechanism. Moreover, we report an association between centrosome clustering ability and the epithelial-to-mesenchymal transition (EMT) and observe that the induction of mesenchymal characteristics in breast cancer cells with centrosome amplification promotes clustering. Furthermore, we unveil hematological malignancies, which lack epithelial characteristics, as the most proficient in centrosome clustering. Finally, we show that acute lymphoblastic leukemia is particularly sensitive to targeting clustering through inhibition of the spindle assembly checkpoint. Our study reveals how centrosome clustering and EMT collaborate to promote carcinogenesis, suggesting new possibilities to treat tumors with low epithelial characteristics, in particular leukemias.

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Section: Expression Levels Of Centrosome Duplication and Clustering G...supporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

High prevalence and dependence of centrosome clustering in mesenchymal tumors and leukemia

Marín

Marteil

Fresmann

et al. 2023

Preprint

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“…In addition, centrosome defects have been shown to promote immune escape of tumor cells, which would lead to tumor deterioration (12). Several studies have shown that CA promotes the development of breast cancer (13)(14)(15)(16). In breast cancer, CA is seen as a driver of chromosomal instability and breast carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Identification of a centrosome-related prognostic signature for breast cancer

Fang

Gao

et al. 2023

Front. Oncol.

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BackgroundAs the major microtubule organizing center in animal cells, the centrosome is implicated with human breast tumor in multiple ways, such as promotion of tumor cell immune evasion. Here, we aimed to detect the expression of centrosome-related genes (CRGs) in normal and malignant breast tissues, and construct a novel centrosome-related prognostic model to discover new biomarkers and screen drugs for breast cancer.MethodsWe collected CRGs from the public databases and literature. The differentially expressed CRGs between normal and malignant breast tissues were identified by the DESeq2. Univariate Cox and LASSO regression analyses were conducted to screen candidate prognostic CRGs and develop a centrosome-related signature (CRS) to score breast cancer patients. We further manipulated and visualized data from TCGA, GEO, IMvigor210, TCIA and TIMER to explore the correlation between CRS and patient outcomes, clinical manifestations, mutational landscapes, tumor immune microenvironments, and responses to diverse therapies. Single cell analyses were performed to investigate the difference of immune cell landscape between high- and low-risk group patients. In addition, we constructed a nomogram to guide clinicians in precise treatment.ResultsA total of 726 CRGs were collected from the public databases and literature. PSME2, MAPK10, EIF4EBP1 were screened as the prognostic genes in breast cancer. Next, we constructed a centrosome-related prognostic signature and validated its efficacy based on the genes for predicting the survival of breast cancer patients. The high-risk group patients had poor prognoses, the area under the ROC curve for 1-, 3-, and 5-year overall survival (OS) was 0.77, 0.67, and 0.65, respectively. The predictive capacity of CRS was validated by other datasets from GEO dataset. In addition, high-risk group patients exhibited elevated level of mutational landscapes and decreased level of immune infiltration, especially T and B lymphocytes. In terms of treatment responses, patients in the high-risk group were found to be resistant to immunotherapy but sensitive to chemotherapy. Moreover, we screened a series of candidate anticancer drugs with high sensitivity in the high-risk group.ConclusionOur work exploited a centrosome-related prognostic signature and developed a predictive nomogram capable of accurately predicting breast cancer OS. The above discoveries provide deeper insights into the vital roles of the centrosome and contribute to the development of personalized treatment for breast cancer.

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“…and regulatory molecules (Cdc2, Cdk1, Plk1, Nek2, etc.) 3 . Although, α-tubulin and β-tubulin are not centrosome markers, but found in the centrosome, because centrosome organizes microtubules made up of α-tubulin and β-tubulin.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, centrosome amplification is closely associated with epithelial to mesenchymal transition (EMT) in aggressive TNBC 3 , 16 , 17 . E-cadherin; a member of the orchestra of EMT is required for centrosome and spindle orientation.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic alterations impede epithelial-mesenchymal transition by modulating centrosome amplification and Myc/RAS axis in triple negative breast cancer cells

Das¹

2023

Sci Rep

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Alterations in centrosome proteins may result in centrosome abnormalities such as disorganized spindles and centrosome amplification, leading to aneuploidy and genomic instability. Centrosomes exhibit unique epigenetic properties in which structural or positional information is propagated through somatic lineage by non-genetic pathways. Excessive centrosome amplification in breast cancer is accompanied by efficient clustering and loss of E-cadherin, indicating an important adaptive mechanism of cancer. This study sought to elucidate the effect of epigenetic alterations on centrosome amplification, epithelial-mesenchymal transition (EMT) and apoptosis in triple negative human breast adenocarcinoma derived MDA-MB-231 cell line. The results obtained here show that siRNA mediated silencing of DNMT1 and specific inhibition of HDAC1 & HDAC2 by Tricostatin A (TSA) synergistically inhibit cell proliferation through modulation of centrosome proteins γ-tubulin, TUBGCP2 and pericentrin. In addition, induction of apoptosis was observed by downregulation of Bcl2, upregulation of Bax and activation of PARP cleavage. Inhibition of EMT was confirmed through upregulation of E-cadherin and downregulation of N-cadherin and vimentin. Similarly, downregulation of Myc, RAS and CDK2, which plays important roles in proliferation and survival, was observed. Nuclear protein analysis revealed downregulation in the nuclear translocation of E2F1, which regulates centrosome amplification and metastasis in breast cancer. In conclusion, this study confirmed the role of epigenetic regulators in centrosome amplification and suggests that inhibition of DNA methylation and histone deacetylation-mediated chromatin remodelling synergistically disrupt EMT through modulation of centrosome amplification and Myc/RAS axis to potentiate apoptosis and attenuate cell proliferation in triple negative breast cancer cells.

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A look into the link between centrosome amplification and breast cancer

Cited by 15 publications

References 175 publications

High prevalence and dependence of centrosome clustering in mesenchymal tumors and leukemia

High prevalence and dependence of centrosome clustering in mesenchymal tumors and leukemia

Identification of a centrosome-related prognostic signature for breast cancer

Epigenetic alterations impede epithelial-mesenchymal transition by modulating centrosome amplification and Myc/RAS axis in triple negative breast cancer cells

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