Ras Signaling in Breast Cancer

Author(s):  
Aree Moon
Keyword(s):  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Patrick D. Rädler ◽  
Barbara L. Wehde ◽  
Aleata A. Triplett ◽  
Hridaya Shrestha ◽  
Jonathan H. Shepherd ◽  
...  

AbstractClaudin-low breast cancer represents an aggressive molecular subtype that is comprised of mostly triple-negative mammary tumor cells that possess stem cell-like and mesenchymal features. Little is known about the cellular origin and oncogenic drivers that promote claudin-low breast cancer. In this study, we show that persistent oncogenic RAS signaling causes highly metastatic triple-negative mammary tumors in mice. More importantly, the activation of endogenous mutant KRAS and expression of exogenous KRAS specifically in luminal epithelial cells in a continuous and differentiation stage-independent manner induces preneoplastic lesions that evolve into basal-like and claudin-low mammary cancers. Further investigations demonstrate that the continuous signaling of oncogenic RAS, as well as regulators of EMT, play a crucial role in the cellular plasticity and maintenance of the mesenchymal and stem cell characteristics of claudin-low mammary cancer cells.


2011 ◽  
Vol 31 (13) ◽  
pp. 2683-2695 ◽  
Author(s):  
S. Sato ◽  
P. C. Trackman ◽  
J. M. Maki ◽  
J. Myllyharju ◽  
K. H. Kirsch ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1610 ◽  
Author(s):  
Antonio Daniel Martinez-Gutierrez ◽  
David Cantú de León ◽  
Oliver Millan-Catalan ◽  
Jossimar Coronel-Hernandez ◽  
Alma D. Campos-Parra ◽  
...  

Breast cancer is the neoplasm with the highest number of deaths in women. Although the molecular mechanisms associated with the development of this tumor have been widely described, metastatic disease has a high mortality rate. In recent years, several studies show that microRNAs or miRNAs regulate complex processes in different biological systems including cancer. In the present work, we describe a group of 61 miRNAs consistently over-expressed in breast cancer (BC) samples that regulate the breast cancer transcriptome. By means of data mining from TCGA, miRNA and mRNA sequencing data corresponding to 1091 BC patients and 110 normal adjacent tissues were downloaded and a miRNA–mRNA network was inferred. Calculations of their oncogenic activity demonstrated that they were involved in the regulation of classical cancer pathways such as cell cycle, PI3K–AKT, DNA repair, and k-Ras signaling. Using univariate and multivariate analysis, we found that five of these miRNAs could be used as biomarkers for the prognosis of overall survival. Furthermore, we confirmed the over-expression of two of them in 56 locally advanced BC samples obtained from the histopathological archive of the National Cancer Institute of Mexico, showing concordance with our previous bioinformatic analysis.


2015 ◽  
Vol 8 (360) ◽  
pp. ec16-ec16
Author(s):  
Leslie K. Ferrarelli
Keyword(s):  

2021 ◽  
pp. 1-12
Author(s):  
Fatemeh Khojasteh Poor ◽  
Mona Keivan ◽  
Mohammad Ramazii ◽  
Farhoodeh Ghaedrahmati ◽  
\unskip\break Amir Anbiyaiee ◽  
...  

Breast cancer (BC) is the most common cancer and the prevalent type of malignancy among women. Multiple risk factors, including genetic changes, biological age, dense breast tissue, and obesity are associated with BC. The mitogen-activated protein kinases (MAPK) signaling pathway has a pivotal role in regulating biological functions such as cell proliferation, differentiation, apoptosis, and survival. It has become evident that the MAPK pathway is associated with tumorigenesis and may promote breast cancer development. The MAPK/RAS/RAF cascade is closely associated with breast cancer. RAS signaling can enhance BC cell growth and progression. B-Raf is an important kinase and a potent RAF isoform involved in breast tumor initiation and differentiation. Depending on the reasons for cancer, there are different strategies for treatment of women with BC. Till now, several FDA-approved treatments have been investigated that inhibit the MAPK pathway and reduce metastatic progression in breast cancer. The most common breast cancer drugs that regulate or inhibit the MAPK pathway may include Farnesyltransferase inhibitors (FTIs), Sorafenib, Vemurafenib, PLX8394, Dabrafenib, Ulixertinib, Simvastatin, Alisertib, and Teriflunomide. In this review, we will discuss the roles of the MAPK/RAS/RAF/MEK/ERK pathway in BC and summarize the FDA-approved prescription drugs that target the MAPK signaling pathway in women with BC.


2020 ◽  
Author(s):  
Shishir Mani Pant ◽  
Topi Tervonen ◽  
Denis Belitskin ◽  
Johanna Englund ◽  
Emmy Verschuren ◽  
...  

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