scholarly journals HIST1H1B Promotes Basal-Like Breast Cancer Progression by Modulating CSF2 Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruocen Liao ◽  
Xingyu Chen ◽  
Qianhua Cao ◽  
Yifan Wang ◽  
Zhaorui Miao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Linker Histone ◽  
Breast Cancer Progression ◽  
Negative Regulator ◽  
Breast Cancer Patients ◽  
Large Tumor ◽  
Molecular Events ◽  
Basal Like Breast Cancer

BackgroundBasal-like breast cancer (BLBC) is associated with a poor clinical outcome; however, the mechanism of BLBC aggressiveness is still unclear. It has been shown that a linker histone functions as either a positive or negative regulator of gene expression in tumors. Here, we aimed to investigate the possible involvement and mechanism of HIST1H1B in BLBC progression.Experimental designWe analyzed multiple gene expression datasets to determine the relevance of HIST1H1B expression with BLBC. We employed quantitative real-time PCR, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the expression of HIST1H1B in human breast cancer. We studied the association of HIST1H1B with CSF2 by ChIP assay. Using tumorigenesis assays, we determine the effect of HIST1H1B expression on tumorigenicity of BLBC cells.ResultsHere, we show that the linker histone HIST1H1B is dramatically elevated in BLBC due to HIST1H1B copy number amplification and promoter hypomethylation. HIST1H1B upregulates colony-stimulating factor 2 (CSF2) expression by binding the CSF2 promoter. HIST1H1B expression promotes, whereas knockdown of HIST1H1B expression suppresses tumorigenicity. In breast cancer patients, HIST1H1B expression is positively correlated with large tumor size, high grade, metastasis and poor survival.ConclusionHIST1H1B contributes to basal-like breast cancer progression by modulating CSF2 expression, indicating a potential prognostic marker and therapeutic target for this disease.

Osteopontin induces multiple changes in gene expression that reflect the six “hallmarks of cancer” in a model of breast cancer progression

2005 ◽  
Vol 43 (4) ◽  
pp. 225-236 ◽  
Author(s):  
Amy C. Cook ◽  
Alan B. Tuck ◽  
Susan McCarthy ◽  
Joel G. Turner ◽  
Rosalyn B. Irby ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Hallmarks Of Cancer

scholarly journals The Calcium-Sensing Receptor (CaSR) Variants at rs1801725 Increase the Risk of Developing Secondary Malignant Cancers

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A268-A269
Author(s):  
Heather K Beasley ◽  
Ky’Era Actkins ◽  
Faucon Annika ◽  
Lea Davis ◽  
Amos M Sakwe
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Preliminary Data ◽  
Breast Cancer Progression ◽  
Secondary Malignancy ◽  
Breast Cancer Patients ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Parathyroid Hormone Related Protein ◽  
Mutational Status

Abstract The dysregulation of systemic calcium homeostasis during malignancy is common in most patients with high-grade tumors. The associated comorbidity is known as cancer-induced hypercalcemia (CIH) which affects up to 30% of cases, in the absence of metastasis. In the course of breast cancer progression, the secretion of parathyroid hormone-related protein (PTHrP) by tumor cells and the associated destruction of bone tissues, leads to a progressive increase in systemic calcium or CIH. The increase in circulating Ca2+ is sensed by the calcium-sensing receptor (CaSR), which plays a significant role in maintaining Ca2+ homeostasis. More than 200 mutations and single nucleotide polymorphisms (SNPs) in the CaSR gene have been described, including the A986S CaSR at rs1801725 and Q1011E CaSR at rs1801726 SNPs with reduced sensitivity to Ca2+. Interestingly, high circulating Ca2+ is associated with aggressive breast tumors in premenopausal women and larger tumors in postmenopausal women; however, the contribution of the CaSR in breast cancer progression remains poorly understood. Unlike SNPs at rs1801726, up to 20% of breast cancer patients with SNPs at rs1801725 may be predisposed to higher circulating Ca2+ in the course of their disease. Since breast cancer frequently metastasizes to Ca2+ rich skeletal tissues, we hypothesize that the development of CIH and subsequent desensitization of the CaSR by sustained high Ca2+ is critical for both the adaptation of TNBC cells to CIH in Ca2+ rich microenvironments and TNBC progression. Our preliminary data reveal that the expression level and mutational status of the CaSR is cell type-specific, and that sustained high Ca2+ desensitizes the receptor, but promotes tumor cell growth and motility. Sustained high Ca2+ also triggers the expression of metastasis promoting genes, including the cancer/testis antigen, MAGEC2, and Plasminogen Activator Inhibitor, PAI-2, potentially via the early response genes FOS/FOSB. In addition, our preliminary data show that the A986S SNP is associated with hypercalcemia, secondary malignancy of bone and respiratory organs, and deficiency of humoral immunity. This study provides novel insights into not only the adaptation of TNBC cells to high circulating Ca2+, but also suggests that mutations of the CaSR at rs1801725 are predictive of the likelihood for metastasis to lungs and bone.

scholarly journals Inhibition of UGT8 suppresses basal-like breast cancer progression by attenuating sulfatide–αVβ5 axis

2018 ◽  
Vol 215 (6) ◽  
pp. 1679-1692 ◽  
Author(s):  
Qianhua Cao ◽  
Xingyu Chen ◽  
Xuebiao Wu ◽  
Ruocen Liao ◽  
Panpan Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Biosynthetic Pathway ◽  
Treatment Options ◽  
Prognostic Indicator ◽  
Inhibitory Effect ◽  
Breast Cancer Patients ◽  
Elevated Expression ◽  
Basal Like Breast Cancer ◽  
Pharmacologic Inhibition

Basal-like breast cancer (BLBC) is associated with a poor clinical outcome as a result of the few treatment options and poor therapeutic response. Here, we report that elevated expression of urine diphosphate–galactose ceramide galactosyltransferase (UGT8) specifically occurs in BLBC and predicts poor prognosis in breast cancer patients. UGT8 expression is transcriptionally up-regulated by Sox10, triggering the sulfatide biosynthetic pathway; increased sulfatide activates integrin αVβ5-mediated signaling that contributes to BLBC progression. UGT8 expression promotes, whereas UGT8 knockdown suppresses tumorigenicity and metastasis. Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which blocks the sulfatide biosynthetic pathway. Significantly, a clinically achievable dosage of ZA exhibits apparent inhibitory effect on migration, invasion, and lung metastasis of BLBC cells. Together, our study suggests that UGT8 is a potential prognostic indicator and druggable target of BLBC and that pharmacologic inhibition of UGT8 by ZA offers a promising opportunity for treating this challenging disease.

scholarly journals Ligand-activated PPARγ downregulates CXCR4 gene expression through a novel identified PPAR response element and inhibits breast cancer progression

Oncotarget ◽  
2016 ◽  
Vol 7 (40) ◽  
pp. 65109-65124 ◽  
Author(s):  
Daniela Rovito ◽  
Giulia Gionfriddo ◽  
Ines Barone ◽  
Cinzia Giordano ◽  
Fedora Grande ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Response Element ◽  
Ppar Response Element
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