scholarly journals Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis

2017 ◽  
Vol 95 (8) ◽  
pp. 873-886 ◽  
Author(s):  
Da-nian Dai ◽  
Yan Li ◽  
Bo Chen ◽  
Yong Du ◽  
Shi-bing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Breast Cancer Cells ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Cysteine Proteases ◽  
Migration And Invasion ◽  
List Type

Abstract Cystatin SN (CST1) belongs to the type 2 cystatin (CST) superfamily, which restricts the proteolytic activities of cysteine proteases. CST1 has been recently considered to be involved in the development of several human cancers. However, the prognostic significance and function of CST1 in breast cancer remains unknown. In the current study, we found that CST1 was generally upregulated in breast cancer at both mRNA and protein level. Furthermore, overall survival (OS) and disease-free survival (DFS) in the low CST1 expression subgroup were significantly superior to the high CST1 expression subgroup (OS, p < 0.001; DFS, p < 0.001), which indicated that CST1 expression level was closely correlated to the survival risk of these patients. Univariate and multivariate analyses demonstrated that CST1 expression was an independent prognostic factor, the same as ER status and nodal status. Next, CST1 overexpression promoted breast cancer cell proliferation, clonogenicity, migration, and invasion abilities. By contrast, knockdown of CST1 attenuated these malignant characteristics in breast cancer cells. Collectively, our study indicates that CST1 cannot only serve as a significant prognostic indicator but also as a potential therapeutic target for breast cancer. Key messages High CST1 expression is negatively correlated with survival of breast cancer patients. CST1 promotes cell proliferation, clone formation, and metastasis in breast cancer cells. CST1 is a novel potential prognostic biomarker and therapeutic target for breast cancer.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

2021 ◽  
pp. 096032712198942
Author(s):  
Xiaoxue Zhang ◽  
Xianxin Xie ◽  
Kuiran Gao ◽  
Xiaoming Wu ◽  
Yanwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

scholarly journals The Effects of Houttuynia cordata Thunb and Piper ribesioides Wall Extracts on Breast Carcinoma Cell Proliferation, Migration, Invasion and Apoptosis

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1196 ◽  
Author(s):  
Subhawat Subhawa ◽  
Teera Chewonarin ◽  
Ratana Banjerdpongchai
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Houttuynia Cordata ◽  
Houttuynia Cordata Thunb

Houttuynia cordata Thunb. (HCT) and Piper ribesioides Wall. (PR) are common herbs that are widely distributed throughout East Asia and possess various biological properties including anti-cancer effects. However, in breast cancer, their mechanisms responsible for anti-carcinogenic effects have not been clarified yet. In this study, the inhibitory effects of HCT and PR ethanolic extracts on breast cancer cell proliferation, migration, invasion and apoptosis were examined. In MCF-7 and MDA-MB-231 cells, HCT and PR extracts at low concentrations can inhibit colony formation and induce G1 cell cycle arrest by downregulating cyclinD1 and CDK4 expression. Additionally, HCT and PR extracts also decreased the migration and invasion of both breast cancer cell lines through inhibition of MMP-2 and MMP-9 secretion. Moreover, the induction of apoptosis was observed in breast cancer cells treated with high concentrations of HCT and PR extracts. Not only stimulated caspases activity, but HCT and PR extracts also upregulated the expression of caspases and pro-apoptotic Bcl-2 family proteins in breast cancer cells. Altogether, these findings provide the rationale to further investigate the potential actions of HCT and PR extracts against breast cancer in vivo.

scholarly journals Axl Phosphorylates Elmo Scaffold Proteins To Promote Rac Activation and Cell Invasion

2014 ◽  
Vol 35 (1) ◽  
pp. 76-87 ◽  
Author(s):  
Afnan Abu-Thuraia ◽  
Rosemarie Gauthier ◽  
Rony Chidiac ◽  
Yoshinori Fukui ◽  
Robert A. Screaton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Nucleotide Exchange

The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved carboxyl-terminal tyrosine residue. Upon Gas6-dependent activation of Axl, endogenous Elmo2 becomes phosphorylated on Tyr-713 and enters into a physical complex with Axl in breast cancer cells. Interfering with Elmo2 expression prevented Gas6-induced Rac1 activation in breast cancer cells. Similarly to blocking of Axl, Elmo2 knockdown or pharmacological inhibition of Dock1 abolishes breast cancer cell invasion. Interestingly, Axl or Elmo2 knockdown diminishes breast cancer cell proliferation. Rescue of Elmo2 knockdown cells with the wild-type protein but not with Elmo2 harboring Tyr-713-Phe mutations restores cell invasion and cell proliferation. These results define a new mechanism by which Axl promotes cell proliferation and invasion and identifies inhibition of the Elmo-Dock pathway as a potential therapeutic target to stop Axl-induced metastases.

scholarly journals ELF5 inhibits migration and invasion of breast cancer cells via regulating CD24 expression

2020 ◽  
Author(s):  
Xinjian Qu ◽  
Qianqian Li ◽  
Simei Tu
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Gene Promoter ◽  
Human Breast Cancer Cell ◽  
Migration And Invasion ◽  
Human Breast ◽  
Cis Element ◽  
Mcf 7

Abstract Objective: E74-like factor five (ELF5) is a basic transcriptional factor that plays a key role in breast tissue and glandular development. However, the molecular mechanism by which ELF5 mediates the biological functions of breast cancer cells has not been elucidated. We hypothesize that ELF5 regulate CD24 transcription though an E26 transforming sequence (ETS) cis-element in the CD24 promoter region.Methods: Human breast cancer cell line MCF-7 was transfected with Myc-ELF5 plasmid in over-expression experiment. T47D cells were transfected with ELF5-shRNA plasmid in knockout experiment. The expression level of ELF5 `protein was analyzed by Western blot. MTT assays and Clonal formation assays were used to assess the proliferation properties of cells. Scratch wound-healing assays were performed to determine cell migration and invasive activities. CD24 protein expression was analysis by flow cytometry. Using the bioinformatics tool JASPAR, we identified high-scoring ETS-like sequences in the CD24 gene promoter. To confirm the ETS, Chromatin immunoprecipitation (ChIP) analysis was used. DNA fragments of a putative or mutated ETS-like sequence were synthesized and ligated into a pGL3 basic plasmid to construct the CD24 promoter luciferase reporter systems which was used to detect ELF5 regulation of CD24 transcriptional activity.Results: In this study, we examined the effect of ELF5 on human breast cancer cell lines MCF-7 and T49D, and confirmed that ELF5 act as a suppressor of cell proliferation, migration and invasion. In further research, the interaction between ELF5 and CD24 was characterized in breast cancer cells. We found that CD24 was a target gene of ELF5 through ChIP-Sequence assays, and proved that ELF5 could bind to ETS cis-element on the proximal promoter of CD24 gene. Importantly, experiments verified that CD24 was upregulated after ELF5 overexpression in MCF-7 cells, while knockdown of CD24 expression caused MCF-7 cells to restore cell proliferation, migration and invasion activity in adaptive ELF5 expression.Conclusions: This study not only found that ELF5 can inhibit cell proliferation, migration and invasion in breast cancer cells, but also found that ELF5 induced CD24 expression by binding to the ETS cis element in the CD24 gene promoter sequence. This study provided a molecular mechanism for ELF5 to inhibit breast cancer from a new perspective, and provided further theoretical support for the treatment and prevention of breast cancer.

scholarly journals Calcium-Sensing Receptor Antagonist NPS-2143 Inhibits Breast Cancer cell Proliferation, Migration and Invasion via Downregulation of p-ERK1/2, Bcl-2 and Integrin β1 and Induces Caspase 3/7 Activation

2021 ◽  
Author(s):  
Mohammad A Y Alqudah ◽  
Marwah Azaizeh ◽  
Aref Zayed ◽  
Leen Asaad
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Caspase 3 ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Calcium Sensing Receptor ◽  
Integrin Β1 ◽  
Calcium Sensing

Purpose: Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the bone. Targeting chemoattractant factors, such as calcium, that are released in response to bone resorption could prevent metastasis and induce apoptosis of cancer cells. In the present study, we investigated the potential caspase 3/7 activation following treatment with a CaSR antagonist, NPS-2143, in breast cancer cells. In addition, the effects of NPS-2143 on breast cancer cell proliferation, migration and invasion were assessed. Methods: Colorimetric MTT assay was used to evaluate cell viability. Apo-one homogeneous caspase-3/7 assay was used to measure caspase 3/7 activities in breast cancer cells. Cell migration and invasion were assessed using scratch wound assay and matrigel invasion chambers, respectively. The protein expressions of p-ERK1/2, integrin β1 and Bcl-2 were evaluated using western blotting. Results: Our study revealed that NPS-2143 significantly reduced cell proliferation with half maximal (50%) inhibitory concentration (IC50) values of 4.08 and 5.71 µM in MDA-MB-231 and MCF-7 cells, respectively. NPS-2143 induced caspase 3/7 activation in MDA-MB-231 breast cancer cells which was accompanied with a remarkable reduction in the expression of Bcl-2 antiapoptotic protein. NPS-2143 suppressed migratory and invasive abilities of MDA-MB-231 cells with a significant reduction in the expression of p-ERK1/2 and integrin β1 proteins. Conclusion: Our study confirms the ability NPS-2143 to suppress proliferative, migratory and invasive effects of breast cancer cells which was accompanied by caspase 3/7 activation and suggests the potential of NPS-2143 as a promising anti-cancer molecule in breast cancer.

Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and In Vitro Studies

2022 ◽  
Vol 22 ◽  
Author(s):  
Wei Shi ◽  
Lu Qi ◽  
Xiong-Bin You ◽  
Yu-Chi Chen ◽  
Yu-Lian Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Shock ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Breast Cancer Cells ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Network Pharmacology ◽  
Cancer Tissue

Background: Shenling Baizhu Powder (SBP), a famous Traditional Chinese Medicine (TCM) formulation, has been widely used in the adjuvant treatment of cancers, including breast cancer. This study aims to identify potential new targets for breast cancer treatment based on the network pharmacology of SBP. Methods: By analyzing the relationship between herbs and target proteins, potential targets of multiple herbs in SBP were identified by network pharmacology analysis. Besides, by comparing the data of breast cancer tissue with normal tissue, upregulated genes in two breast cancer expression profiles were found. Thereafter, the expression level and prognosis of activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) were further analyzed in breast cancer by bioinformatics analysis, and the network module of AHSA1 binding protein was constructed. Furthermore, the effect of knocking down AHSA1 on the proliferation, migration, and invasion of breast cancer cells was verified by MTT, clone formation assay, and transwell assay. Results: Vascular endothelial growth factor A (VEGFA), intercellular adhesion molecule 1 (ICAM1), chemokine (C-X-C motif) ligand 8 (CXCL8), AHSA1, and serpin family E member 1 (SERPINE1) were associated with multiple herbs in SBP. AHSA1 was remarkably upregulated in breast cancer tissues and positively correlated with poor overall survival and disease metastasis-free survival. Furthermore, knockdown of AHSA1 significantly inhibited the migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells but had no obvious effect on proliferation. In addition, among the proteins that bind to AHSAl, the network composed of proteasome, chaperonin, and heat shock proteins is closely connected, and these proteins are associated with poor prognosis in a variety of cancers. Conclusion: AHSA1 is positively correlated with breast cancer progression and might act as a novel therapeutic target for breast cancer.

scholarly journals miR-301b-3p Regulates Breast Cancer Cell Proliferation, Migration, and Invasion by Targeting NR3C2

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yaohua Fan ◽  
Yan Li ◽  
Yuzhang Zhu ◽  
Guiping Dai ◽  
Dongjuan Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Cancer Cell Proliferation

Objectives. Breast cancer is the most common malignant tumor among females, and miRNAs have been reported to play an important regulatory role in breast cancer progression. This study aimed to explore the function and underlying molecular mechanism of miR-301b-3p in breast cancer. Methods. Differential analysis and survival analysis were performed based on the data accessed from the TCGA-BRCA dataset for identification of the target miRNA. Bioinformatics analysis was conducted to predict the downstream target gene of the miRNA. Real-time quantitative PCR was carried out to detect the expression of miR-301b-3p and nuclear receptor subfamily 3 group C member 2 (NR3C2). Western blot was used to assess the protein expression of NR3C2. Cell counting kit-8 assay was performed to evaluate the proliferation of breast cancer cells. Transwell assay was conducted to determine the migratory and invasive abilities of breast cancer cells. Dual-luciferase reporter assay was employed to verify the targeting relationship between miR-301b-3p and NR3C2. Results. miR-301b-3p was elevated in breast cancer cell lines and promoted cell proliferation, migration, and invasion in terms of its biological function in breast cancer. NR3C2 was validated as a direct target of miR-301b-3p via bioinformatics analysis and dual-luciferase reporter assay, and NR3C2 was downregulated in breast cancer cell lines. The rescue experiment indicated that NR3C2 was involved in the mechanism by which miR-301b-3p regulated the malignant phenotype of breast cancer cells. Conclusion. The present study revealed for the first time that miR-301b-3p could foster breast cancer cell proliferation, migration, and invasion by targeting NR3C2, unveiling that miR-301b-3p is a novel carcinogen in breast cancer.

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