scholarly journals BHMPS Inhibits Breast Cancer Migration and Invasion by Disrupting Rab27a-Mediated EGFR and Fibronectin Secretion

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 373
Author(s):  
Jeong-In Park ◽  
Kyung-Hee Song ◽  
Seong-Mook Kang ◽  
Jeeyong Lee ◽  
Seong-Jun Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Biological Significance ◽  
Growth Factor Receptor ◽  
Migration And Invasion ◽  
Kinase Activation ◽  
Mesenchymal Transition ◽  
Proximity Ligation ◽  
Cancer Migration ◽  
Epidermal Growth

Our previous work demonstrated that (E)-N-benzyl-6-(2-(3, 4-dihydroxybenzylidene) hydrazinyl)-N-methylpyridine-3-sulfonamide (BHMPS), a novel synthetic inhibitor of Rab27aSlp(s) interaction, suppresses tumor cell invasion and metastasis. Here, we aimed to further investigate the mechanisms of action and biological significance of BHMPS. BHMPS decreased the expression of epithelial-mesenchymal transition transcription factors through inhibition of focal adhesion kinase and c-Jun N-terminal kinase activation, thereby reducing the migration and invasion of breast cancer. Additionally, knockdown of Rab27a inhibited tumor migration, with changes in related signaling molecules, whereas overexpression of Rab27a reversed this phenomenon. BHMPS effectively prevented the interaction of Rab27a and its effector Slp4, which was verified by co-localization, immunoprecipitation, and in situ proximity ligation assays. BHMPS decreased the secretion of epidermal growth factor receptor and fibronectin by interfering with vesicle trafficking, as indicated by increased perinuclear accumulation of CD63-positive vesicles. Moreover, administration of BHMPS suppressed tumor growth in Rab27a-overexpressing MDA-MB-231 xenograft mice. These findings suggest that BHMPS may be a promising candidate for attenuating tumor migration and invasion by blocking Rab27a-mediated exocytosis.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

scholarly journals MicroRNA-1246 Suppresses the Metastasis of Breast Cancer Cells by Targeting the DRAK1A/PGRN Axis to Prevent the Epithelial-Mesenchymal Transition

2021 ◽  
Author(s):  
Pan Wang ◽  
Wenju Chen ◽  
Yaqiong Zhang ◽  
Qianyi Zhong ◽  
Zhaoyun Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell ◽  
Novel Target

Abstract Objective. Breast cancer is one of the most common malignant and highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-1246, play important roles in various types of malignant cancers, including triple-negative breast cancer (TNBC). However, the biological role of miR-1246 in TNBC has not yet been fully elucidated. In this study, we studied the role of miR-1246 in the occurrence and development of TNBC and its mechanism of action.Methods. Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays were performed to observe the effects of miR-1246 on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers was detected by western blotting. Dual luciferase reporter assays were performed to determine whether DYRK1A is a novel target of miR-1246. In addition, an immunoprecipitation experiment was performed to verify the binding of DYRK1A to PGRN. Rescue experiments were performed to determine whether DYRK1A is a novel target of miR-1246 and whether miR-1246 suppresses the metastasis of breast cancer cells by targeting the DRAK1A/PGRN axis to prevent the epithelial-mesenchymal transition.Results. Our results show that miR‑1246 suppresses the proliferation, migration, and invasion of TNBC cells and that DYRK1A is a novel target of miR-1246. MiR‑1246 plays a suppressive role in the regulation of the EMT of TNBC cells by targeting DYRK1A. DYRK1A mediates the metastasis of triple-negative breast cancer via activation of the EMT. We identified PGRN as a novel DYRK1A-interacting protein. DYRK1A and PGRN act together to regulate the occurrence and development of breast cancer through miR-1246.Conclusion. miR-1246 attenuates TNBC cell invasion and the EMT by targeting the DRAK1A/PGRN axis. Our data suggest that miR‑1246 may be used to develop novel early-stage diagnostic and therapeutic strategies for TNBC.

scholarly journals LINC00665 promotes breast cancer progression through regulation of the miR-379-5p/LIN28B axis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei Ji ◽  
Yu-Ling Diao ◽  
Yi-Ran Qiu ◽  
Jie Ge ◽  
Xu-Chen Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Normal Breast ◽  
Breast Cancer Progression ◽  
Migration And Invasion ◽  
Breast Tumorigenesis ◽  
Mesenchymal Transition ◽  
Tumorigenesis And Progression ◽  
Mirna Sponges

AbstractBreast cancer is the most common malignant tumor among women worldwide. Although increasing evidence indicates that long noncoding RNAs (lncRNAs) play critical roles during breast tumorigenesis and progression, the involvement of most lncRNAs in breast cancer remains largely unknown. In the current study, we demonstrated that LINC00665 promotes breast cancer cell proliferation, migration, and invasion. Accumulating evidence indicates that many lncRNAs can function as endogenous miRNA sponges by competitively binding common miRNAs. In this study, we demonstrated that LINC00665 functions as a sponge for miR-379-5p, reducing the ability of miR-379-5p to repress LIN28B. LINC00665 promoted breast cancer progression and induced an epithelial–mesenchymal transition-like phenotype via the upregulation of LIN28B expression. Clinically, LINC00665 expression was increased but miR-379-5p expression was decreased in breast cancer tissues compared with that in normal breast tissues in the TCGA database. Furthermore, the expression of LINC00665 was negatively related with miR-379-5p expression. Collectively, our results reveal the LINC00665–miR-379-5p–LIN28B axis and shed light on breast cancer therapy.

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