scholarly journals Role of Heparan Sulfate 2-O-Sulfotransferase in Prostate Cancer Cell Proliferation, Invasion, and Growth Factor Signaling

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Brent W. Ferguson ◽  
Sumana Datta
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Cancer Progression ◽  
Metastatic Potential ◽  
Growth Factor Signaling ◽  
Cancer Cell Proliferation ◽  
Determining Factors ◽  
Proliferation And Invasion

Heparan-sulfate proteoglycans (HSPGs) are required for maximal growth factor signaling in prostate cancer progression. The degree of sulfate modification on the covalently attached heparan sulfate (HS) chains is one of the determining factors of growth factor-HSPG interactions. Sulfate groups are transferred to HS chains via a series of O-sulfotransferases. In the present study, we demonstrate that Heparan sulfate 2-O-sulfotransferase (2OST) is essential for maximal proliferation and invasion of prostate cancer cells in the LNCaP-C4-2B model. We also show that a decrease in invasion due to 2OST siRNA is associated with an increase in actin and E-cadherin accumulation at the cell surface. 2OST expression correlates with increasing metastatic potential in this model. We demonstrate that 2OST expression is upregulated by the stress-inducible transcription factors HIF1α, ATF2, and NFκB. Chromatin immunoprecipitation analysis suggests that HIF1αand ATF2 act directly on the 2OST promoter, while NFκB acts indirectly.

scholarly journals δ-Catenin Participates in EGF/AKT/p21Waf Signaling and Induces Prostate Cancer Cell Proliferation and Invasion

2021 ◽  
Vol 22 (10) ◽  
pp. 5306
Author(s):  
Yingjie Shen ◽  
Hyoung Jae Lee ◽  
Rui Zhou ◽  
Hangun Kim ◽  
Gen Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Nuclear Accumulation ◽  
Cancer Cell Proliferation ◽  
Prostate Cancer Progression ◽  
Key Factor ◽  
Proliferation And Metastasis ◽  
First Time ◽  
Proliferation And Invasion ◽  
Potential Therapeutics

Prostate cancer (PCa) is the second most leading cause of death in males. Our previous studies have demonstrated that δ-catenin plays an important role in prostate cancer progression. However, the molecular mechanism underlying the regulation of δ-catenin has not been fully explored yet. In the present study, we found that δ-catenin could induce phosphorylation of p21Waf and stabilize p21 in the cytoplasm, thus blocking its nuclear accumulation for the first time. We also found that δ-catenin could regulate the interaction between AKT and p21, leading to phosphorylation of p21 at Thr-145 residue. Finally, EGF was found to be a key factor upstream of AKT/δ-catenin/p21 for promoting proliferation and metastasis in prostate cancer. Our findings provide new insights into molecular controls of EGF and the development of potential therapeutics targeting δ-catenin to control prostate cancer progression.

scholarly journals Cytoneme-mediated signaling essential for tumorigenesis

2018 ◽  
Author(s):  
Sol Fereres ◽  
Ryo Hatori ◽  
Makiko Hatori ◽  
Thomas B. Kornberg
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Normal Development ◽  
Signaling Proteins ◽  
Growth Factor Signaling ◽  
Loss Of Function ◽  
Paracrine Signaling

ABSTRACTCommunication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor models. We tested several genetic loss-of-function conditions that impair cytoneme-mediated signaling. diaphanous, Neuroglian, SCAR, capricious are genes that cytonemes require during normal development. Genetic inhibition of cytonemes restored apical basal polarity to tumor cells, reduced tumor growth, and increased organism survival. These findings suggest that cytonemes traffic the signaling proteins that move between tumor and stromal cells, and that cytoneme-mediated signaling is required for tumor growth and malignancy.SummaryEssential cytonemes for paracrine signaling in Drosophila tumors

scholarly journals Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-βand IGF Signaling

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Chung Lee ◽  
Zhenyu Jia ◽  
Farah Rahmatpanah ◽  
Qiang Zhang ◽  
Xiaolin Zi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Reciprocal Relationship ◽  
Cancer Development ◽  
Igf Signaling

This review postulates the role of transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between TGF-βand IGF signaling occupies a central part in this stromal-epithelial interaction. An increase in TGF-βand IGF signaling will set off the imbalance of this relationship and will lead to cancer development. A continuous input from TGF-βand IGF in the tumor microenvironment will result in cancer progression. Understanding of these events can help prevention, diagnosis, and therapy of prostate cancer.

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