scholarly journals c-Abl Mediated Tyrosine Phosphorylation of Aha1 Activates Its Co-chaperone Function in Cancer Cells

Cell Reports ◽  
2015 ◽  
Vol 12 (6) ◽  
pp. 1006-1018 ◽  
Author(s):  
Diana M. Dunn ◽  
Mark R. Woodford ◽  
Andrew W. Truman ◽  
Sandra M. Jensen ◽  
Jacqualyn Schulman ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tyrosine Phosphorylation ◽  
Chaperone Function

scholarly journals Ganglioside GD1a inhibits HGF-induced motility and scattering of cancer cells through suppression of tyrosine phosphorylation of c-Met

2001 ◽  
Vol 94 (3) ◽  
pp. 328-334 ◽  
Author(s):  
Sumiko Hyuga ◽  
Nana Kawasaki ◽  
Masashi Hyuga ◽  
Miyako Ohta ◽  
Rie Shibayama ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tyrosine Phosphorylation ◽  
Ganglioside Gd1a

scholarly journals IRF9 and unphosphorylated STAT2 cooperate with NF-κB to drive IL6 expression

2018 ◽  
Vol 115 (15) ◽  
pp. 3906-3911 ◽  
Author(s):  
Jing Nan ◽  
Yuxin Wang ◽  
Jinbo Yang ◽  
George R. Stark
Keyword(s):  
Dna Binding ◽  
Cancer Cells ◽  
Tyrosine Phosphorylation ◽  
High Expression ◽  
Response Element ◽  
Il6 Gene ◽  
Binding Subunit

In response to IFNβ, the IL6 gene is activated, modestly at early times by ISGF3 (IRF9 plus tyrosine-phosphorylated STATs 1 and 2), and strongly at late times by U-ISGF3 (IRF9 plus U-STATs 1 and 2, lacking tyrosine phosphorylation). A classical IFN-stimulated response element (ISRE) at −1,513 to −1,526 in the human IL6 promoter is required. Pretreating cells with IFNβ or increasing the expression of U-STAT2 and IRF9 exogenously greatly enhances IL6 expression in response to the classical NF-κB activators IL1, TNF, and LPS. U-STAT2 binds tightly to IRF9, the DNA binding subunit of ISGF3, and also to the p65 subunit of NF-κB. Therefore, as shown by ChIP analyses, U-STAT2 can bridge the ISRE and κB elements in the IL6 promoter. In some cancer cells, the protumorigenic activation of STAT3 will be enhanced by the increased synthesis of IL6 that is facilitated by high expression of U-STAT2 and IRF9.

Tyrosine phosphorylation of HDAC3 by Src kinase mediates proliferation of HER2-positive breast cancer cells

2018 ◽  
Vol 234 (5) ◽  
pp. 6428-6436 ◽  
Author(s):  
Jaesung Seo ◽  
Garam Guk ◽  
Seung-Ho Park ◽  
Mi-Hyeon Jeong ◽  
Ji-Hoon Jeong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tyrosine Phosphorylation ◽  
Breast Cancer Cells ◽  
Src Kinase ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Sensitivity to Romidepsin Cytotoxicity Depends on STAT3-Dependent Metabolic Reprogramming of Cancer Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3599-3599
Author(s):  
Maher Abdul-Hay ◽  
Daniel Gough ◽  
David Levy
Keyword(s):  
Cancer Cells ◽  
Tyrosine Phosphorylation ◽  
Conflicts Of Interest ◽  
Global Analysis ◽  
Active Form ◽  
Disease Free Survival ◽  
Cancer Therapeutics ◽  
Serine Phosphorylation ◽  
Metabolic Reprogramming ◽  
Cytokine Signaling

Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and accounts for approximately 80% of cases in this group. Even with the best treatment currently available, there is a very high rate of relapse and mortality. The five-year survival rates are only 24% with relapse rates up to 78%. Accordingly the search for a better understanding of the molecular biology and genetics underlying AML is essential in our quest to find treatments that achieve a better overall survival. Signal transduction and activator of transcription protein 3 (STAT3) has been implicated in many human cancers, including AML; up to 50% of AML patients display enhanced tyrosine phosphorylation of STAT3. Constitutively active STAT3 has also been correlated with shorter disease free survival in AML patients. Accumulating clinical, genetic and biochemical data implicate STAT3 in the majority of human malignancies, indicating that it is essential for tumor initiation and/or maintenance. The best understood tumorigenic activity of STAT3 depends on its tyrosine phosphorylation, mostly due to response to increased secretion of cytokines or mutations in oncogenic tyrosine kinases. However, serine phosphorylation of STAT proteins in the absence of tyrosine phosphorylation or increased cytokine signaling has also been implicated in human leukemias. Moreover, it has recently been found that STAT3 contributes to tumor metabolic reprogramming in a cytokine-independent manner through a novel mitochondrial function that was noted to cause myeloproliferative disease-like in mice models. Methods: We conducted a global analysis of metabolites whose abundance in cancer cells depended on the presence of mitochondrial STAT3, assessed by LC/HPLC coupled to mass spectrometry. This analysis identified glutathione (GSH) levels as being dependent on mitochondrial STAT3, along with multiple intermediaries in the GSH biosynthetic pathway. GSH provides essential reducing capacity in cells and its levels are often elevated in cancer. Romidepsin (Depsipeptide) is an HDAC inhibitor that must be converted to an active form by disulfide reduction via glutathione, originally characterized for its cytotoxicity against Ras-transformed cells. We have found enhanced Romidepsin toxicity in STAT3-containing cancer cells, which correlates with the presence of increased GSH and reduced reactive oxygen species (ROS). We found that the enzymes in the GSH synthetic pathway are coordinately regulated by STAT3. We also found that Romidepsin increases STAT3 expression at both the mRNA and the protein levels and we are analyzing the mechanism by which STAT3 is affected by Romidepsin. Conclusion: Enhanced Romidepsin toxicity was found in STAT3-containing cancer cells. These STAT3-containinng cells were noted to have higher glutathione synthase expression, which plays a major role in the GSH production in the gamma glutamyl cycle. This could potentially explain the higher GSH levels noted in the presence of STAT3-contianing cells. These studies hopefully will aid in the design of cancer therapeutics that target STAT3-dependent processes that contribute to oncogenesis and could lead to have better treatments available in myeloid diseases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Involvement of Src in the Adaptation of Cancer Cells under Microenvironmental Stresses

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
A. K. M. Mahbub Hasan ◽  
Takashi Ijiri ◽  
Ken-ichi Sato
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine Phosphorylation ◽  
Cellular Functions ◽  
Specific Behavior ◽  
Protein Tyrosine ◽  
Health And Disease ◽  
The Relationship

Protein-tyrosine phosphorylation, which is catalyzed by protein-tyrosine kinase (PTK), plays a pivotal role in a variety of cellular functions related to health and disease. The discovery of the viral oncogene Src (v-Src) and its cellular nontransforming counterpart (c-Src), as the first example of PTK, has opened a window to study the relationship between protein-tyrosine phosphorylation and the biology and medicine of cancer. In this paper, we focus on the roles played by Src and other PTKs in cancer cell-specific behavior, that is, evasion of apoptosis or cell death under stressful extracellular and/or intracellular microenvironments (i.e., hypoxia, anoikis, hypoglycemia, and serum deprivation).

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