Constitutive c-Met phosphorylation mediates growth in the absence of EGFR kinase activity in breast cancer cells dependent on EGFR expression for growth.

2009 ◽  
Author(s):  
KL Mueller ◽  
R Haddad ◽  
JL Boerner
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Egfr Expression ◽  
Egfr Kinase ◽  
Met Phosphorylation

Neddylation controls basal MKK7 kinase activity in breast cancer cells

Oncogene ◽  
2015 ◽  
Vol 35 (20) ◽  
pp. 2624-2633 ◽  
Author(s):  
T Zhu ◽  
J Wang ◽  
Y Pei ◽  
Q Wang ◽  
Y Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Activity

scholarly journals Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yanli Bi ◽  
Longyuan Gong ◽  
Pengyuan Liu ◽  
Xiufang Xiong ◽  
Yongchao Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Nuclear Translocation ◽  
Extracellular Signals ◽  
Consensus Binding Sequence ◽  
Binding Sequence

AbstractErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.

scholarly journals Constitutive p21-activated Kinase (PAK) Activation in Breast Cancer Cells as a Result of Mislocalization of PAK to Focal Adhesions

2004 ◽  
Vol 15 (6) ◽  
pp. 2965-2977 ◽  
Author(s):  
Mary R. Stofega ◽  
Luraynne C. Sanders ◽  
Elisabeth M. Gardiner ◽  
Gary M. Bokoch
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Rho Gtpases ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Focal Adhesions ◽  
Breast Cancer Cell Lines ◽  
Cytoskeletal Remodeling ◽  
P21 Activated Kinase ◽  
Pak Kinase

Cytoskeletal remodeling is critical for cell adhesion, spreading, and motility. p21-activated kinase (PAK), an effector molecule of the Rho GTPases Rac and Cdc42, has been implicated in cytoskeletal remodeling and cell motility. PAK kinase activity and subcellular distribution are tightly regulated by rapid and transient localized Rac and Cdc42 activation, and by interactions mediated by adapter proteins. Here, we show that endogenous PAK is constitutively activated in certain breast cancer cell lines and that this active PAK is mislocalized to atypical focal adhesions in the absence of high levels of activated Rho GTPases. PAK localization to focal adhesions in these cells is independent of PAK kinase activity, NCK binding, or GTPase binding, but requires the association of PAK with PIX. Disruption of the PAK–PIX interaction with competitive peptides displaces PAK from focal adhesions and results in a substantial reduction in PAK hyperactivity. Moreover, disruption of the PAK–PIX interaction is associated with a dramatic decrease of PIX and paxillin in focal adhesions, indicating that PAK localization to these structures via PIX is required for the maintenance of paxillin- and PIX-containing focal adhesions. Abnormal regulation of PAK localization and activity may contribute to the tumorigenic properties of certain breast cancer cells.

scholarly journals MEKK2 regulates paxillin ubiquitylation and localization in MDA-MB 231 breast cancer cells

2014 ◽  
Vol 464 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Magdalene Ameka ◽  
Michael P. Kahle ◽  
Mathew Perez-Neut ◽  
Saverio Gentile ◽  
Ahmed A. Mirza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumour Cell ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Focal Adhesions ◽  
Scaffold Protein ◽  
Physical Association

MEKK2 associates with the scaffold protein paxillin in tumour cell focal adhesions, promoting paxillin ubiquitylation and redistribution to cytoplasm. MEKK2 silencing prolongs paxillin retention in focal adhesions. MEKK2 requires both kinase activity and physical association with paxillin to promote ubiquitylation.

scholarly journals MiR-218-5p promotes breast cancer progression via LRIG1

2021 ◽  
Author(s):  
Mingping Qian ◽  
Hui Xu ◽  
Hongming Song ◽  
Hao Xi ◽  
Lin Fang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Human Breast ◽  
Egfr Expression ◽  
Breast Tissues ◽  
Mcf 7

Abstract Background : MiR-218-5p is a small non-coding RNA acting as either oncogenes or tumor suppressor genes in human cancer. The expression levels of some miRNAs in human breast cancer plays a potential role in disease pathogenesis. Methods : Thirty pairs of invasive ductal carcinoma and adjacent specimens were included in the study. Breast tissues cell lines MCF-7 and MDA-MB-231 were identified as a breast cancer research cell line. MiR-218-5p mimics, miR-218-5p inhibitor, or negative controls were transfected. Specific antibodies were probed with LRIG1, ErbB2, and EGFR. Proliferation, migration, cell cycle and apoptosis, dual-luciferase reporter assay and immunohistochemistry were used to analyze miR-218-5p、LRIG1 and so on. Results : It was shown that miR-218-5p expression was higher in 30 breast cancer specimens than adjacent normal breast tissues. In human breast cancer cells MCF-7 and MDA-MB-231, restoring miR-218-5p promoted cell proliferation and migration and inhibited cell apoptosis and cell cycle arrest in the G1 stage. Luciferase assays indicated miR-218-5p could bind with its putative target site in the 3'-untranslated region (3'-UTR) of LRIG1. RT-qPCR, western blot, and immunocytochemistry analyses all indicated miR-218-5p overexpression results in LRIG1 downregulation at the mRNA and protein levels. ErbB2 and EGFR were found to be downstream effectors of miR-218-5p. Conclusion : MiR-218-5p promotes ErbB2 and EGFR expression by inhibiting LRIG1 in breast cancer cells, which suggests miR-218-5p and LRIG1 may act as an oncogene in breast cancer and it could be used as a therapeutic target for breast cancer treatments. Keywords: Breast cancer; miR-218-5p; LRIG1; Oncogene

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