scholarly journals FAM96A and FAM96B Suppress Breast Cancer Proliferation and Migration via the Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Di-Di Zhang ◽  
Xiao-Lin Sun ◽  
Zhao-Yuan Liang ◽  
Li-Na Zhang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Invasion And Migration ◽  
And Migration

Abstract Background: Family with sequence similarity 96 member A and B (FAM96A and FAM96B) are two highly conserved homologous proteins belonging to MIP18 family. Many studies have shown that FAM96A and FAM96B play many different functions mainly through interacting with other different proteins. Recently, several studies show that FAM96A and FAM96B are significantly down-regulated compared in human gastrointestinal stromal tumors, colon cancer, liver cancer and gastric cancer with corresponding normal tissues. However, the molecular regulatory mechanisms of FAM96A and FAM96B in breast cancer development and metastasis are still unclear. In this work, we aimed to explore the molecular mechanisms of FAM96A and FAM96B in breast cancer progression.Methods: We used specific siRNAs to down-regulate FAM96A and FAM96B expression, and used recombinant plasmids to up-regulate FAM96A and FAM96B expression in breast cancer cells. Cell proliferation was measured using MTT and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry analysis. Wound healing and transwell assays were used to examine cell migration and invasion abilities. The relationships among FAM96A/B, EMT and Wnt/β-catenin signaling pathway were determined by analyzing the expression changes of classical markers and biological functional changes after XAV-939 inhibitor treatment. Results: We found that FAM96A and FAM96B expression in breast cancer was down-regulated. FAM96A/B overexpression suppressed breast cancer cell proliferation, invasion and migration, induced cell apoptosis and led to cell cycle arrested in G0/G1 phase. Conversely, FAM96A/B knockdown exhibited the opposite effects on breast cancer cells. Moreover, our data demonstrated that FAM96A/B overexpression suppressed EMT and Wnt/β-catenin signaling pathway, while FAM96A/B knockdown showed the promoting effects on EMT and Wnt/β-catenin signaling pathway in breast cancer cells. Furthermore, a Wnt pathway inhibitor, XAV-939 treatment reversed the promoting effects of FAM96A and FAM96B knockdown on breast cancer cell proliferation, invasion and migration.Conclusions: Our findings revealed that FAM96A and FAM96B may act as tumor suppressor genes and inhibit breast cancer progression via modulating the Wnt/β-catenin pathway, which can provide the potential markers for the diagnosis and treatment of breast cancer.

scholarly journals Oroxylin A Suppresses the Cell Proliferation, Migration, and EMT via NF-κB Signaling Pathway in Human Breast Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
XiaoHu Sun ◽  
Xinzhong Chang ◽  
Yunhua Wang ◽  
Boyang Xu ◽  
Xuchen Cao
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Inflammatory Factors ◽  
Human Breast ◽  
Oroxylin A ◽  
Invasion And Migration ◽  
And Migration

Oroxylin A is a natural extract and has been reported to have a remarkable anticancer function. However, the mechanism of its anticancer activity remains not quite clear. In this study, we examined the inhibiting effects of Oroxylin A on breast cancer cell proliferation, migration, and epithelial-mesenchymal transition (EMT) and its possible molecular mechanism. The cytoactive and inflammatory factors were analyzed via Cell Counting Kit-8 assay and ELISA assay, respectively. Flow cytometry and western blotting were used to assess the cell proliferation. In addition, a wound healing assay and transwell assay were used to detect cell invasion and migration. qRT-PCR and western blot were employed to determine the effect of Oroxylin A on the EMT formation. Moreover, expression level of protein related to NF-κB signaling pathway was determined by western blot. The results revealed that Oroxylin A attenuated the cytoactivity of MDA-MB-231 cells in a dose- and a time-dependent manner. Moreover, cell proliferation, invasion, and migration of breast cancer cells were inhibited by Oroxylin A compared to the control. The mRNA and protein expression levels of E-cadherin were remarkably increased while N-cadherin and Vimentin remarkably decreased. Besides, Oroxylin A suppressed the expression of inflammatory factors and NF-κB activation. Furthermore, we also found that supplement of TNF-α reversed the effects of Oroxylin A on the cell proliferation, invasion, migration, and EMT in breast cancer cells. Taken together, our results suggested that Oroxylin A inhibited the cell proliferation, invasion, migration, and EMT through inactivating NF-κB signaling pathway in human breast cancer cells. These findings strongly suggest that Oroxylin A could be a therapeutic potential candidate for the treatment of breast cancer.

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 Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Travis B. Salisbury ◽  
Gary Z. Morris ◽  
Justin K. Tomblin ◽  
Ateeq R. Chaudhry ◽  
Carla R. Cook ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Aryl Hydrocarbon

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly (P<0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity.

scholarly journals Alternative MyD88 -Cyclin D1 signaling in breast cancer cells regulates TLR3 mediated cell proliferation

2020 ◽  
Author(s):  
Aradhana Singh ◽  
Ranjitsinh Devkar ◽  
Anupam Basu
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Adjuvant Therapy ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Surface Localization ◽  
Tlr3 Signaling

AbstractTLR3 mediated apoptotic changes in cancer cells are well documented and hence several synthetic ligands of TLR3 are being used for adjuvant therapy. But there are reports showing contradictory effect of TLR3 signaling which includes our previous report that had shown cell proliferation following surface localization of TLR 3. However, the underlying mechanism of cell surface localization of TLR3 and subsequent cell proliferation lacks clarity. This study addresses TLR3 ligand mediated signaling cascade that regulates a proliferative effect in breast cancer cells (MDA MB 231 and T47D) challenged with TLR3 ligand in the presence of MyD88 inhibitor. Evidences were obtained using immunoblotting, co-immunoprecipitation, confocal microscopy, Immunocytochemistry, ELISA, and flowcytometry. Results had revealed that TLR3 ligand treatment significantly enhanced breast cancer cell proliferation marked by an upregulated expression of cyclinD1 but the same were suppressed by addition of MyD88 inhibitor. Also, expression of IRAK1-TRAF6-TAK1 were altered in the given TLR3-signaling pathway. Inhibition of MyD88 disrupted the downstream adaptor complex and mediated signaling through TLR3-MyD88-NF-κB (p65)-IL6-Cyclin D1 pathway. TLR3 mediated alternative signaling of the TLR3-MyD88-IRAK1-TRAF6-TAK1-TAB1-NF-κB axis leads to upregulation of IL6 and cyclinD1. This response is hypothesized to be via the MyD88 gateway that culminates in proliferation of breast cancer cells. Overall, this study provides first comprehensive evidence on involvement of canonical signaling of TLR3 using MyD88 - Cyclin D1 mediated breast cancer cell proliferation. The findings elucidated herein will provide valuable insights into understand the TLR3 mediated adjuvant therapy in cancer.

scholarly journals Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation

2020 ◽  
Vol 21 (8) ◽  
pp. 2906
Author(s):  
Yih Ho ◽  
Zi-Lin Li ◽  
Ya-Jung Shih ◽  
Yi-Ru Chen ◽  
Kuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Plasma Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Integrin Αvβ3 ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation

Hormones and their receptors play an important role in the development and progression of breast cancer. Hormones regulate the proliferation of breast cancer cells through binding between estrogen or progestins and steroid receptors that may reside in the cytoplasm or be transcriptionally activated as steroid–protein nuclear receptor complexes. However, receptors for nonpeptide hormones also exist in the plasma membrane. Via those receptors, hormones are able to stimulate breast cancer cell proliferation when activated. Integrins are heterodimeric structural proteins of the plasma membrane. Their primary functions are to interact with extracellular matrix proteins and growth factors. Recently, integrin αvβ3 has been identified as a receptor for nonpeptide hormones, such as thyroid hormone and dihydrotestosterone (DHT). DHT promotes the proliferation of human breast cancer cells through binding to integrin αvβ3. A receptor for resveratrol, a polyphenol stilbene, also exists on this integrin in breast cancer cells, mediating the anti-proliferative, pro-apoptotic action of the compound in these cells. Unrelated activities of DHT and resveratrol that originate at integrin depend upon downstream stimulation of mitogen-activated protein kinase (MAPK, ERK1/2) activity, suggesting the existence of distinct, function-specific pools of ERK1/2 within the cell. This review will discuss the features of these receptors in breast cancer cells, in turn suggesting clinical applications that are based on the interactions of resveratrol/DHT with integrin αvβ3 and other androgen receptors.

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