scholarly journals N‑glycosylation and receptor tyrosine kinase signaling affect claudin‑3 levels in colorectal cancer cells

2020 ◽  
Author(s):  
Amelia P�rez ◽  
J�ssica Andrade‑Da‑Costa ◽  
Waldemir De Souza ◽  
Michelle De Souza Ferreira ◽  
Mariana Boroni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Receptor Tyrosine Kinase ◽  
Kinase Signaling ◽  
Tyrosine Kinase Signaling ◽  
Colorectal Cancer Cells

scholarly journals Araguspongine C Induces Autophagic Death in Breast Cancer Cells through Suppression of c-Met and HER2 Receptor Tyrosine Kinase Signaling

Marine Drugs ◽  
2015 ◽  
Vol 13 (1) ◽  
pp. 288-311 ◽  
Author(s):  
Mohamed Akl ◽  
Nehad Ayoub ◽  
Hassan Ebrahim ◽  
Mohamed Mohyeldin ◽  
Khaled Orabi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Receptor Tyrosine Kinase ◽  
Breast Cancer Cells ◽  
Kinase Signaling ◽  
Her2 Receptor ◽  
Tyrosine Kinase Signaling

scholarly journals mTORC1-independent autophagy regulates receptor tyrosine kinase phosphorylation in colorectal cancer cells via an mTORC2-mediated mechanism

2017 ◽  
Vol 24 (6) ◽  
pp. 1045-1062 ◽  
Author(s):  
Aikaterini Lampada ◽  
James O'Prey ◽  
Gyorgy Szabadkai ◽  
Kevin M Ryan ◽  
Daniel Hochhauser ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Receptor Tyrosine Kinase ◽  
Colorectal Cancer Cells ◽  
Kinase Phosphorylation

scholarly journals Cell surface integrin α5ß1 clustering negatively regulates receptor tyrosine kinase signaling in colorectal cancer cells via glycogen synthase kinase 3

2021 ◽  
Author(s):  
Alina Starchenko ◽  
Ramona Graves-Deal ◽  
Douglas Brubaker ◽  
Cunxi Li ◽  
Yuping Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factors ◽  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Receptor Tyrosine Kinase ◽  
Negative Regulator ◽  
Mouse Tumor ◽  
Functional Responses ◽  
Colorectal Cancer Cells

Abstract As a key process within the tissue microenvironment, integrin signaling can influence cell functional responses to growth factor stimuli. We show here that clustering of integrin α5ß1 at the plasma membrane of colorectal cancer-derived epithelial cells modulates their ability to respond to stimulation by receptor tyrosine kinase (RTK)-activating growth factors EGF, NRG and HGF, through GSK3-mediated suppression of Akt pathway. We observed that integrin α5ß1 is lost from the membrane of poorly organized human colorectal tumors and that treatment with the integrin-clustering antibody P4G11 is sufficient to induce polarity in a mouse tumor xenograft model. While adding RTK growth factors (EGF, NRG and HGF) to polarized colorectal cancer cells induced invasion and loss of monolayer formation in 2D and 3D, this pathological behavior could be blocked by P4G11. Phosphorylation of ErbB family members as well as MET following EGF, NRG and HGF treatment was diminished in cells pretreated with P4G11. Focusing on EGFR, we found that blockade of integrin α5ß1 increased EGFR phosphorylation. Since activity of multiple downstream kinase pathways were altered by these various treatments, we employed computational machine learning techniques to ascertain the most important effects. Partial least-squares discriminant analysis identified GSK3 as a major regulator of EGFR pathway activities influenced by integrin α5ß1. Moreover, we used partial correlation analysis to examine signaling pathway crosstalk downstream of EGF stimulation and found that integrin α5ß1 acts as a negative regulator of the AKT signaling cascade downstream of EGFR, with GSK3 acting as a key mediator. We experimentally validated these computational inferences by confirming that blockade of GSK3 activity is sufficient to induce loss of polarity and increase of oncogenic signaling in the colonic epithelial cells.

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