scholarly journals Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression

Oncogene ◽  
2012 ◽  
Vol 31 (47) ◽  
pp. 4960-4966 ◽  
Author(s):  
M-L Nairismägi ◽  
A Vislovukh ◽  
Q Meng ◽  
G Kratassiouk ◽  
C Beldiman ◽  
...  
2009 ◽  
Vol 69 (14) ◽  
pp. 5946-5953 ◽  
Author(s):  
Narasimharao V. Marella ◽  
Kishore S. Malyavantham ◽  
Jianmin Wang ◽  
Sei-ichi Matsui ◽  
Ping Liang ◽  
...  

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Michelle M. Martinez‐Montemayor ◽  
Robert J. Schneider ◽  
Chunling Zhang ◽  
Jorge Andrade ◽  
Ivette J. Suarez‐Arroyo

2016 ◽  
Vol 113 (3) ◽  
pp. 638-643 ◽  
Author(s):  
Sait Ozturk ◽  
Panagiotis Papageorgis ◽  
Chen Khuan Wong ◽  
Arthur W. Lambert ◽  
Hamid M. Abdolmaleky ◽  
...  

Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss of function of metastasis suppressor genes is a major rate-limiting step in breast cancer progression that prevents the formation of new colonies at distal sites. However, the discovery of new metastasis suppressor genes in breast cancer using genomic efforts has been slow, potentially due to their primary regulation by epigenetic mechanisms. Here, we report the use of model cell lines with the same genetic lineage for the identification of a novel metastasis suppressor gene, serum deprivation response (SDPR), localized to 2q32-33, a region reported to be associated with significant loss of heterozygosity in breast cancer. In silico metaanalysis of publicly available gene expression datasets suggests that the loss of expression of SDPR correlates with significantly reduced distant-metastasis–free and relapse-free survival of breast cancer patients who underwent therapy. Furthermore, we found that stable SDPR overexpression in highly metastatic breast cancer model cell lines inhibited prosurvival pathways, shifted the balance of Bcl-2 family proteins in favor of apoptosis, and decreased migration and intravasation/extravasation potential, with a corresponding drastic suppression of metastatic nodule formation in the lungs of NOD/SCID mice. Moreover, SDPR expression is silenced by promoter DNA methylation, and as such it exemplifies epigenetic regulation of metastatic breast cancer progression. These observations highlight SDPR as a potential prognostic biomarker and a target for future therapeutic applications.


2021 ◽  
Vol 10 ◽  
Author(s):  
Chengqin Wang ◽  
Runze Zhang ◽  
Xiao Wang ◽  
Yan Zheng ◽  
Huiqing Jia ◽  
...  

Breast cancer is the most common malignant tumors in women. Kinesin family member 3B (KIF3B) is a critical regulator in mitotic progression. The objective of this study was to explore the expression, regulation, and mechanism of KIF3B in 103 cases of breast cancer tissues, 35 metastatic lymph nodes and breast cancer cell lines, including MDA-MB-231, MDA-MB-453, T47D, and MCF-7. The results showed that KIF3B expression was up-regulated in breast cancer tissues and cell lines, and the expression level was correlated with tumor recurrence and lymph node metastasis, while knockdown of KIF3B suppressed cell proliferation, migration, and invasion both in vivo and in vitro. In addition, UALCAN analysis showed that KIF3B expression in breast cancer is increased, and the high expression of KIF3B in breast cancer is associated with poor prognosis. Furthermore, we found that silencing of KIF3B decreased the expression of Dvl2, phospho-GSK-3β, total and nucleus β-catenin, then subsequent down-regulation of Wnt/β-catenin signaling target genes such as CyclinD1, C-myc, MMP-2, MMP-7 and MMP-9 in breast cancer cells. In addition, KIF3B depletion inhibited epithelial mesenchymal transition (EMT) in breast cancer cells. Taken together, our results revealed that KIF3B is up-regulated in breast cancer which is potentially involved in breast cancer progression and metastasis. Silencing KIF3B might suppress the Wnt/β-catenin signaling pathway and EMT in breast cancer cells.


Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1582 ◽  
Author(s):  
Amira F. Mahdi ◽  
Beatrice Malacrida ◽  
Joanne Nolan ◽  
Mary E. McCumiskey ◽  
Anne B. Merrigan ◽  
...  

When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.


Author(s):  
Chuanbo Xu ◽  
Haitao Yu ◽  
Xianghua Yin ◽  
Jishi Zhang ◽  
Chunlin Liu ◽  
...  

Abstract We investigated the expression and functions of circular RNA (circRNA) circNINL and miR-921 in breast cancer (BC) in this study. We found that the expression of circNINL increased while the expression of miR-921 decreased in BC tissues and cell lines, and their anomalous expressions were associated with malignant features and poor prognostic of BC. Then, we demonstrated that circNINL could interact with miR-921 and facilitate BC cells malignant process including proliferation acceleration, migration enhancement and apoptosis evasion via sponging miR-921 in vitro. Further investigations revealed that circNINL/miR-921 axis could mediate the expression of ADAM9 which was a direct target of miR-921. In addition, we exhibited that ADAM9 may activate β-catenin signaling by interacting with E-cadherin. We presented the vital roles of circNINL/miR-921/ADAM9/β-catenin signaling in the progression of BC.


2020 ◽  
Author(s):  
Jonathan Kulwatno ◽  
Xiangyu Gong ◽  
Rebecca DeVaux ◽  
Jason I. Herschkowitz ◽  
Kristen Lynn Mills

ABSTRACTDuctal carcinoma in situ (DCIS) is a pre-cancerous stage breast cancer, where abnormal cells are contained within the duct, but have not invaded into the surrounding tissue. However, only 30-40% of DCIS cases are likely to progress into an invasive ductal carcinoma (IDC), while the remainder are innocuous. Since little is known about what contributes to the transition from DCIS to IDC, clinicians and patients tend to opt for treatment, leading to concerns of overdiagnosis and overtreatment. In vitro models are currently being used to probe how DCIS transitions into IDC, but many models do not take into consideration the macroscopic tissue architecture and the biomechanical properties of the microenvironment. Here, we developed an organotypic mammary duct model by molding a channel within a collagen matrix and lining it with a basement membrane. By adjusting the concentration of collagen, we effectively modulated the stiffness and morphological properties of the matrix and examined how an assortment of breast cells responded to changing density and stiffness of the matrix. We first validated the model using two established, phenotypically divergent breast cancer cell lines by demonstrating the ability of the cells to either invade (MDA-MB-231) or cluster (MCF7). We then examined how cells of the isogenic MCF10 series—spanning the range from healthy to aggressive—behaved within our model and observed distinct characteristics of breast cancer progression such as hyperplasia and invasion, in response to collagen concentration. Our results show that the model can recapitulate different stages of breast cancer progression and that the MCF10 series is adaptable to physiologically relevant in vitro studies, demonstrating the potential of both the model and cell lines to elucidate key factors that may contribute to understanding the transition from DCIS to IDC.IMPACT STATEMENTThe success of early preventative measures for breast cancer has left patients susceptible to overdiagnosis and overtreatment. Limited knowledge of factors driving an invasive transition has inspired the development of in vitro models that accurately capture this phenomenon. However, current models tend to neglect the macroscopic architecture and biomechanical properties of the mammary duct. Here, we introduce an organotypic model that recapitulates the cylindrical geometry of the tissue and the altered stroma seen in tumor microenvironments. Our model was able to capture distinct features associated with breast cancer progression, demonstrating its potential to uncover novel insights into disease progression.


2014 ◽  
Author(s):  
Mattia Capulli ◽  
Adriano Angelucci ◽  
Anna Teti ◽  
Patrizia Sanita ◽  
Luca Ventura ◽  
...  

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