| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Attarha, S., et al.
(författare)
-
PKN I modulates TGF beta and EGF signaling in HEC-I-A endometrial cancer cell line
- 2014
-
Ingår i: Oncotargets and Therapy. - : Informa UK Limited. - 1178-6930. ; 7, s. 1397-1408
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The response of cells to TGF beta and EGF is mediated by a network of various intracellular regulators. The signaling crosstalk between different regulators is of key importance for tumorigenesis. The crosstalk may explain the modulation of cellular responses to the same regulator by another signaling molecule. As PKN1-a serine/threonine kinase implicated in tumorigenesis was identified as potential crosstalk node for TGF beta and EGF signaling, the cellular functions that may be affected by PKN1 in a crosstalk of TGF beta and EGF were explored. Methods: To investigate the contribution of PKN1 to TGF beta and EGF signaling, transiently PKN1-transfected HEC-1-A endometrial cancer cells were generated and subjected to treatment with TGF beta, EGF, and their combination. Proliferation, apoptosis, invasion, wound healing, and migration assays were performed. The impact of PKN1 on the expression and phosphorylation of intracellular proteins was monitored by immunoblotting. Results: It was demonstrated that PKN1 modulated the responses of HEC-A-1 endometrial cancer cells to TGF beta and EGF PKN1 had an inhibitory effect on the stimulation of cell migration, and PKN1 kinase activity was required for the inhibitory effect of TGF beta and EGF on cell proliferation and invasiveness. It was observed that phosphorylation of Smad2, FAK, and Erk1/2 correlated with responses of the cells to TGF beta and EGE Conclusion: PKN1 modulates TGF beta- and EGF-dependent regulation of cell proliferation, migration, and invasiveness, and therefore is a component of the network signaling downstream of IGO and EGE
|
|
| 5. |
|
|
| 6. |
- Busker, S., et al.
(författare)
-
Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death
- 2020
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:12
-
Tidskriftsartikel (refereegranskat)abstract
- Because of its key role in cancer development and progression, STAT3 has become an attractive target for developing new cancer therapeutics. While several STAT3 inhibitors have progressed to advanced stages of development, their underlying biology and mechanisms of action are often more complex than would be expected from specific binding to STAT3. Here, we have identified and optimized a series of compounds that block STAT3-dependent luciferase expression with nanomolar potency. Unexpectedly, our lead compounds did not bind to cellular STAT3 but to another prominent anticancer drug target, TrxR1. We further identified that TrxR1 inhibition induced Prx2 and STAT3 oxidation, which subsequently blocked STAT3-dependent transcription. Moreover, previously identified inhibitors of STAT3 were also found to inhibit TrxR1, and likewise, established TrxR1 inhibitors block STAT3-dependent transcriptional activity. These results provide new insights into the complexities of STAT3 redox regulation while highlighting a novel mechanism to block aberrant STAT3 signaling in cancer cells.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Saini, Ravi Kanth Rao, et al.
(författare)
-
Proteomics of dedifferentiation of SK-N-BE2 neuroblastoma cells
- 2014
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 454:1, s. 202-209
-
Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma develops through processes which include cellular dedifferentiation. Ability of tumors to form spheroids is one of the manifestations of dedifferentiation and carcinogenic transformation. To study mechanisms of dedifferentiation of neuroblastoma cells, we generated spheroids and performed a proteomics study to compare the spheroids with parental SK-N-BE2 cells. We observed that dedifferentiation induced extensive changes in the proteome profiles of the cells, which affected more than 30% of detected cellular proteins. Using mass spectrometry, we identified 239 proteins affected by dedifferentiation into spheroids as compared to the parental cells. These proteins represented such regulatory processes as transcription, cell cycle regulation, apoptosis, cell adhesion, metabolism, intracellular transport, stress response, and angiogenesis. A number of potent regulators of stemness, differentiation and cancer were detected as subnetworks formed by the identified proteins. Our validation tissue microarray study of 30 neuroblastoma cases confirmed that two of the identified proteins, DISC1 and DNA-PKcs, had their expression increased in advanced malignancies. Thus, our report unveiled extensive changes of the cellular proteome upon dedifferentiation of neuroblastoma cells, indicated top subnetworks and clusters of molecular mechanisms involved in dedifferentiation, and provided candidate biomarkers for clinical studies. (C) 2014 Elsevier Inc. All rights reserved.
|
|
