Dual function of MAZ mediated by FOXF2 in basal-like breast cancer: Promotion of proliferation and suppression of progression

Yu, Zi Han; Lun, Shu Min; He, Rui; Tian, Hong; Huang, Huan; Wang, Qing Shan; Li, Xiao Qing; Feng, Yuanming

doi:10.1016/j.canlet.2017.05.020

Cited by 32 publications

(28 citation statements)

References 34 publications

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“…S10). but suppresses progression (40). Based on these results (37-40), we proposed that FBXO22 may help to establish the primary tumor colonies at the early stages of tumorigenesis by enhancing tumor cell viability and growth.…”

Section: Fbxo22 Promotes Snail Degradation In a Gsk3b Phosphorylationmentioning

confidence: 93%

FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer Progression

et al. 2018

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The molecular underpinnings behind malignant progression of breast cancer from a localized lesion to an invasive and ultimately metastatic disease are incompletely understood. Here, we report that F-box only protein 22 (FBXO22) plays a dual role in mammary tumorigenesis and metastasis. FBXO22 was upregulated in primary breast tumors and promoted cell proliferation and colony formation and xenograft tumorigenicity Surprisingly, FBXO22 suppressed epithelial-mesenchymal transition (EMT), cell motility, and invasiveness and metastatic lung colonization Clinical data showed that expression levels of FBXO22 were associated with favorable clinical outcomes, supporting the notion that metastasis, rather than primary cancer, is the major determinant of the mortality of patients with breast cancer. Mechanistic investigations further revealed that FBXO22 elicits its antimetastatic effects by targeting SNAIL, a master regulator of EMT and breast cancer metastasis, for ubiquitin-mediated proteasomal degradation in a glycogen synthase kinase 3β phosphorylation-dependent manner. Importantly, expression of SNAIL rescued FBXO22-mediated suppression of EMT, cell migration, and invasion. A patient-derived tryptophan-to-arginine mutation at residue 52 (W52R) within the F-box domain impaired FBXO22 binding to the SKP1-Cullin1 complex and blocked FBXO22-mediated SNAIL degradation, thus abrogating the ability of FBXO22 to suppress cell migration, invasion, and metastasis. Collectively, these findings uncover an unexpected dual role for FBXO22 in mammary tumorigenesis and metastatic progression and delineate the mechanism of an oncogenic mutation of FBXO22 in breast cancer progression. These findings highlight the paradoxical roles of FBXO22 in breast cancer, as it promotes breast tumor cell proliferation but prevents EMT and metastasis. .

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Section: Fbxo22 Promotes Snail Degradation In a Gsk3b Phosphorylationmentioning

confidence: 93%

FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer Progression

et al. 2018

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“…Several oncogenes, including MYC, HRAS, PPARG, TSG101, VEGFA, CAV1, PTHR1, NOS3, MYB, and hTER, are transcriptionally regulated by MAZ (Jun Song et al, 2001;Lee et al, 2016;Ray et al, 2002). Deregulated expression of MAZ appears to participate in the development and/or progress various tissue malignancies including the breast, thyroid, hepatocellular and urothelial cancers (Jiao et al, 2013;Dudas et al, 2008;Yu et al, 2017;Ray, 2011;Zhu et al, 2016)…”

Section: Functionmentioning

confidence: 99%

Section: Breast Cancermentioning

confidence: 99%

“…Based on data sets in Gene expression-based Outcome for Breast Cancer Online (GOBO, http://co.bmc.lu.se/gobo/), the expression of MAZ is found to be correlated with distant metastasis-free survival (DMFS) in basal-like breast cancer (BLBC) patients and that the under-expression of MAZ is involved in the metastatic spread of BLBC (Yu et al, 2017). Based on these finding, it was suggested that MAZ plays dual roles in basal-like breast cancer (BLBC): it suppresses cancer progression but promotes cellular proliferation (Yu et al, 2017). Experimental studies using model cell lines derived from breast cancer indeed suggest that MAZ promotes cell proliferation yet it suppresses the aggressiveness of BLBC by controlling the transition toward a more mesenchymal phenotype (Yu et al, 2017;Ray, 2011).…”

Section: Breast Cancermentioning

confidence: 99%

“…Based on these finding, it was suggested that MAZ plays dual roles in basal-like breast cancer (BLBC): it suppresses cancer progression but promotes cellular proliferation (Yu et al, 2017). Experimental studies using model cell lines derived from breast cancer indeed suggest that MAZ promotes cell proliferation yet it suppresses the aggressiveness of BLBC by controlling the transition toward a more mesenchymal phenotype (Yu et al, 2017;Ray, 2011).…”

Section: Breast Cancermentioning

confidence: 99%

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MAZ (MYC Associated Zinc Finger Protein)

Karakaya¹,

Muyan²

2018

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Myc-associated zinc finger protein (MAZ), also known as serum amyloid A-activating factor 1 (SAF1), Pur-1 or Zif87, is ubiquitously expressed in various tissues. MAZ is a transcription factor with six Cys2His2-type zinc finger motifs at the carboxylterminus that interact with a permutation of the GGGAGGG sequence motif present in GC-rich promoter regions of target genes, likely through DNA unfolding of G-quadruplex structures to modulate gene expressions. MAZ is also suggested to participate in transcription termination and polyadenylation. Deregulated expression of MAZ is reported to correlate with various tissue malignancies that include the breast, thyroid, hepatocellular and urothelial cancers.

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Construction of a breast cancer prognosis model based on alternative splicing and immune infiltration

et al. 2022

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Background Breast cancer (BC) is the most common malignancy among women in the world. Alternative splicing (AS) is an important mechanism for regulating gene expression and producing proteome diversity, which is closely related to tumorigenesis. Understanding the role of AS in BC may be helpful to reveal new therapeutic targets for clinical interventions. Methods RNA-seq, clinical and AS data of TCGA-BRCA were downloaded from TCGA and TCGA SpliceSeq databases. AS events associated with prognosis were filtered by univariate Cox regression. The AS risk model of BC was built by Lasso regression, random forest and multivariate Cox regression. The accuracy of the AS risk model and clinicopathological factors were evaluated by time-dependent receiver operating characteristic (ROC) curves. The significant factors were used to construct the nomogram model. Tumor microenvironment analysis, immune infiltration and immune checkpoint analysis were performed to show the differences between the high and low AS risk groups. The expression differences of genes of AS events constituting the risk model in tumor tissues and normal tissues were analyzed, the genes with significant differences were screened, and their relationship with prognosis, tumor microenvironment, immune infiltration and immune checkpoint were analyzed. Finally, Pearson correlation analysis was used to calculate the correlation coefficient between splicing factors (SF) and prognostic AS events in TCGA-BRCA. The results were imported into Cytoscape, and the associated network was constructed. Results A total of 21,232 genes had 45,421 AS events occurring in TCGA-BRCA, while 1604 AS events were found to be significantly correlated with survival. The BRCA risk model consisted of 5 AS events, (TTC39C|44853|AT*− 2.67) + (HSPBP1|52052|AP*− 4.28) + (MAZ|35942|ES*2.34) + (ANK3|11845|AP*1.18) + (ZC3HAV1|81940|AT*1.59), which were confirmed to be valuable for predicting BRCA prognosis to a certain degree, including ROC curve, survival analysis, tumor microenvironment analysis, immune infiltration and immune checkpoint analysis. Based on this, we constructed a nomogram prediction model composed of clinicopathological features and the AS risk signature. Furthermore, we found that MAZ was a core gene indicating the connection of tumor prognosis and AS events. Ultimately, a network of SF-AS regulation was established to reveal the relationship between them. Conclusions We constructed a nomogram model combined with clinicopathological features and AS risk score to predict the prognosis of BC. The detailed analysis of tumor microenvironment and immune infiltration in the AS risk model may further reveal the potential mechanisms of BC recurrence and development.

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Dual function of MAZ mediated by FOXF2 in basal-like breast cancer: Promotion of proliferation and suppression of progression

Cited by 32 publications

References 34 publications

FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer Progression

FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer Progression

MAZ (MYC Associated Zinc Finger Protein)

Construction of a breast cancer prognosis model based on alternative splicing and immune infiltration

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