CUL4B Promotes Breast Carcinogenesis by Coordinating with Transcriptional Repressor Complexes in Response to Hypoxia Signaling Pathway

Huang, Wei; Zhang, Jingyao; Huo, Miaomiao; Gao, Jie; Yang, Tianshu; Yin, Xin; Wang, Pei; Leng, Shuai; Feng, Dandan; Chen, Yang; Yang, Yang; Wang, Yan

doi:10.1002/advs.202001515

Cited by 20 publications

(10 citation statements)

References 84 publications

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“…Moreover, HDAC2 also promoted IFNg-induced PD-L1 expression to enhance antitumor immunity and tumor proliferation and metastasis (37). More importantly, our recent study demonstrated that the COPS5-associated protein CUL4B could interact with HDAC-containing complexes to promote EMT and stem cell production in breast cancer (38). Additionally, we reported that an epigenetic small-molecule inhibitor of HDACs, PCI-24781, could target RGS2 to reduce cell proliferation, metastasis, and differentiation, resulting in cell death during breast cancer progression (39).…”

Section: Discussionmentioning

confidence: 94%

Identification of Key Transcription Factors and Immune Infiltration Patterns Associated With Breast Cancer Prognosis Using WGCNA and Cox Regression Analysis

et al. 2021

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Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among women worldwide. Therefore, the need for effective breast cancer treatment is urgent. Transcription factors (TFs) directly participate in gene transcription, and their dysregulation plays a key role in breast cancer. Our study identified 459 differentially expressed TFs between tumor and normal samples from The Cancer Genome Atlas database. Based on gene expression analysis and weighted gene co-expression network analysis, the co-expression yellow module was found to be integral for breast cancer progression. A total of 121 genes in the yellow module were used for function enrichment. To further confirm prognosis-related TFs, COX regression and LASSO analyses were performed; consequently, a prognostic risk model was constructed, and its validity was verified. Ten prognosis-related TFs were identified according to their expression profile, survival probability, and target genes. COPS5, HDAC2, and NONO were recognized as hub TFs in breast cancer. These TFs were highly expressed in human breast cancer cell lines and clinical breast cancer samples; this result was consistent with the information from multiple databases. Immune infiltration analysis revealed that the proportions of resting dendritic and mast cells were greater in the low-risk group than those in the high-risk group. Thus, in this study, we identified three hub biomarkers related to breast cancer prognosis. The results provide a framework for the co-expression of TF modules and immune infiltration in breast cancer.

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Section: Discussionmentioning

confidence: 94%

Identification of Key Transcription Factors and Immune Infiltration Patterns Associated With Breast Cancer Prognosis Using WGCNA and Cox Regression Analysis

et al. 2021

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“…Several transcriptional factors, such as Slug, Twist, and ZEB1, have been reported to play a vital function in EMT ( Kurppa et al, 2020 ; Dufourt et al, 2021 ; Huang et al, 2021 ). Slug is one of the critical regulators which lead to EMT and is closely related to cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

PPA1 Promotes Breast Cancer Proliferation and Metastasis Through PI3K/AKT/GSK3β Signaling Pathway

Guo

Liang

et al. 2021

Front. Cell Dev. Biol.

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Breast cancer is the most common malignancy among women. Inorganic pyrophosphatase 1 (PPA1) is a multifunctional protein involved in the development of several tumors. However, the role of PPA1 in breast cancer progression remains unclear. In this study, we found that PPA1 was highly expressed in breast cancer compared to its levels in normal breast tissue and that it was correlated with breast cancer clinicopathological characteristics, as well as poor survival in breast cancer patients. Silencing PPA1 restrained breast cancer proliferation and metastasis by regulating Slug-mediated epithelial-mesenchymal transition (EMT). Opposite results were observed following PPA1 overexpression. In addition, investigation of the underlying mechanism demonstrated that PPA1 ablation led to decrease phosphatidylinositol 3 kinase (PI3K) phosphorylation levels and attenuate phosphorylated AKT and glycogen synthase kinase-3 β (GSK3β), while ectopic PPA1 expression had the opposite effects. Moreover, PI3K inhibitors suppress the signaling pathways mediating the effects of PPA1 on breast cancer, resulting in tumor growth and metastasis suppression in vitro and in vivo. In summary, our results verify that PPA1 can act as an activator of PI3K/AKT/GSK3β/Slug-mediated breast cancer progression and that it is a potential therapeutic target for the inhibition of tumor progression.

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“…Otto Warburg proposed the relationship between Hif-1α and cancer in 1923 as the “Warburg effect” to explain cells surviving under hypoxic conditions. Hif-1α can act as a transcription factor to transactivate downstream effectors to accumulate CUL4B levels in breast cancer, consequently suppressing epithelial-related factors, such as E-cadherin and AXIN2, by cooperating with ZEB2 and Snail to promote metastasis [ 195 ]. In addition, cells in an environment of hypoxia have changes in their activity of metabolism-related enzymes [ 196 ].…”

Section: Defined Emt Molecules In Cancermentioning

confidence: 99%

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

Hsu

Chang

et al. 2021

Biomedicines

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Epithelial and mesenchymal transition mechanisms continue to occur during the cell cycle and throughout human development from the embryo stage to death. In embryo development, epithelial-mesenchymal transition (EMT) can be divided into three essential steps. First, endoderm, mesoderm, and neural crest cells form, then the cells are subdivided, and finally, cardiac valve formation occurs. After the embryonic period, the human body will be subjected to ongoing mechanical stress or injury. The formation of a wound requires EMT to recruit fibroblasts to generate granulation tissues, repair the wound and re-create an intact skin barrier. However, once cells transform into a malignant tumor, the tumor cells acquire the characteristic of immortality. Local cell growth with no growth inhibition creates a solid tumor. If the tumor cannot obtain enough nutrition in situ, the tumor cells will undergo EMT and invade the basal membrane of nearby blood vessels. The tumor cells are transported through the bloodstream to secondary sites and then begin to form colonies and undergo reverse EMT, the so-called “mesenchymal-epithelial transition (MET).” This dynamic change involves cell morphology, environmental conditions, and external stimuli. Therefore, in this manuscript, the similarities and differences between EMT and MET will be dissected from embryonic development to the stage of cancer metastasis.

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CUL4B Promotes Breast Carcinogenesis by Coordinating with Transcriptional Repressor Complexes in Response to Hypoxia Signaling Pathway

Cited by 20 publications

References 84 publications

Identification of Key Transcription Factors and Immune Infiltration Patterns Associated With Breast Cancer Prognosis Using WGCNA and Cox Regression Analysis

Identification of Key Transcription Factors and Immune Infiltration Patterns Associated With Breast Cancer Prognosis Using WGCNA and Cox Regression Analysis

PPA1 Promotes Breast Cancer Proliferation and Metastasis Through PI3K/AKT/GSK3β Signaling Pathway

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

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