Constitutively Activated Stat3 Induces Tumorigenesis and Enhances Cell Motility of Prostate Epithelial Cells through Integrin β6

ABSTRACT The persistent activation of signal transducer and activator of transcription 3 (Stat3) is a common feature of prostate cancer. However, little is known about the Stat3 targets that may mediate prostate tumorigenesis. The introduction of an activating mutant form of Stat3 (Stat3-C) into immortalized prostate epithelial cells resulted in tumorigenesis. Stat3-C-expressing cells had decreased E-cadherin levels, increased numbers of lamellipodia and stress fibers, and enhanced migratory capacities compared to vector control-expressing cells, with a concomitant increase in the expression of integrin β6 and its ligand, fibronectin (FN). Exogenously added FN increased cellular migration, with a concomitant loss of E-cadherin expression. The blockade of integrin αvβ6 in Stat3-C-expressing cells inhibited migration, increased E-cadherin levels, and reduced colony formation in soft agar. These results demonstrate the sufficiency of constitutively activated Stat3 in mediating prostate tumorigenesis and identify novel Stat3 targets that are involved in promoting cell migration and transformation.

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Oncostatin M induces tumorigenic properties in non-transformed human prostate epithelial cells, in part through activation of signal transducer and activator of transcription 3 (STAT3)

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.03.056 ◽

2018 ◽

Vol 498 (4) ◽

pp. 769-774 ◽

Cited By ~ 6

Author(s):

Simona Sterbova ◽

Terese Karlsson ◽

Emma Persson

Keyword(s):

Epithelial Cells ◽

Oncostatin M ◽

Human Prostate ◽

Signal Transducer ◽

Prostate Epithelial Cells ◽

Transcription 3

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E-cadherin expression and PSA secretion in human prostate epithelial cells

Urological Research ◽

10.1007/s002400100188 ◽

2001 ◽

Vol 29 (4) ◽

pp. 287-292 ◽

Cited By ~ 4

Author(s):

Diane Krill ◽

Angela Thomas ◽

Su-Ping Wu ◽

Rajiv Dhir ◽

Michael J. Becich

Keyword(s):

Epithelial Cells ◽

Human Prostate ◽

Prostate Epithelial Cells ◽

E Cadherin

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E-cadherin-mediated survival of androgen-receptor-expressing secretory prostate epithelial cells derived from a stratified in vitro differentiation model

Journal of Cell Science ◽

10.1242/jcs.054502 ◽

2010 ◽

Vol 123 (2) ◽

pp. 266-276 ◽

Cited By ~ 29

Author(s):

L. E. Lamb ◽

B. S. Knudsen ◽

C. K. Miranti

Keyword(s):

Androgen Receptor ◽

Epithelial Cells ◽

In Vitro Differentiation ◽

Prostate Epithelial Cells ◽

Differentiation Model ◽

E Cadherin

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Correlation between the Expression of Interleukin-6, STAT3, E-Cadherin and N-Cadherin Protein and Invasiveness in Nonfunctional Pituitary Adenomas

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0039-1700499 ◽

2019 ◽

Author(s):

Xiaoxu Shen ◽

Qi Liu ◽

Jian Xu ◽

Yang Wang

Keyword(s):

Pituitary Adenoma ◽

Correlation Analysis ◽

Pituitary Adenomas ◽

Signal Transducer ◽

Epithelial Cadherin ◽

Nonfunctional Pituitary Adenomas ◽

Transcription 3 ◽

Spearman’S Correlation ◽

E Cadherin

Abstract Objective This study aimed to investigate the expression of interleukin (IL)-6, signal transducer and activator of transcription 3 (STAT3), epithelial-cadherin (E- cadherin) and neural-cadherin (N-cadherin) proteins in nonfunctional pituitary adenomas, and their correlation with invasiveness. Method Thirty cases of nonfunctional pituitary adenoma pathological wax specimens were selected from our hospital, including 20 cases of invasive nonfunctional pituitary adenoma (INFPA) and 10 noninvasive nonfunctional pituitary adenomas (NNFPAs). Envision was used to detect IL-6, STAT3, E-cadherin , and N-cadherin in specimens. Statistical methods were used to analyze the correlation between the four proteins and the Knosp classification of nonfunctional pituitary adenomas. Result IL-6 and STAT3 were highly expressed in INFPAs but poorly expressed in NNFPAs. E-cadherin expression in INFPAs was lower than that in NNFPAs. N-cadherin was positive or strongly positive in both groups. Spearman's correlation analysis showed that the expression of IL-6 and STAT3 was positively correlated with Knosp's classification, whereas the expression of E-cadherin was negatively correlated with Knosp classification. Meanwhile, the expression of N-cadherin was not correlated with Knosp's classification. Conclusion The expression of the IL-6, STAT3, E-cadherin proteins were associated nonfunctional pituitary adenomas. However, the expression of N-cadherin was not correlated with nonfunctional pituitary adenomas.

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EGF promotes the shedding of soluble E-cadherin in an ADAM10-dependent manner in prostate epithelial cells

Cellular Signalling ◽

10.1016/j.cellsig.2011.10.004 ◽

2012 ◽

Vol 24 (2) ◽

pp. 532-538 ◽

Cited By ~ 26

Author(s):

Magdalena M. Grabowska ◽

Brindar Sandhu ◽

Mark L. Day

Keyword(s):

Epithelial Cells ◽

Dependent Manner ◽

Prostate Epithelial Cells ◽

E Cadherin

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Regulation of Differentiation of HC11 Mouse Breast Epithelial Cells by the Signal Transducer and Activator of Transcription-3

Anticancer Research ◽

10.21873/anticanres.13401 ◽

2019 ◽

Vol 39 (6) ◽

pp. 2749-2756

Author(s):

MAXIMILLIAN NIIT ◽

MULU GELETU ◽

ZAID TAHA ◽

ROZANNE ARULANANDAM ◽

JAMAICA CASS ◽

...

Keyword(s):

Epithelial Cells ◽

Signal Transducer ◽

Breast Epithelial Cells ◽

Breast Epithelial ◽

Transcription 3

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Reducing Selenoprotein F Promotes the Transformation of Immortalized Prostate Epithelial Cells

Current Developments in Nutrition ◽

10.1093/cdn/nzaa067_036 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1809-1809

Author(s):

Lenny Hong ◽

Mostafa Elhodaky ◽

Shrinidhi Kadkol ◽

Alan Diamond

Keyword(s):

Prostate Cancer ◽

Epithelial Cells ◽

Cancer Progression ◽

Tca Cycle ◽

Soft Agar ◽

Metabolic Shift ◽

Normal Prostate ◽

Funding Sources ◽

Prostate Cells ◽

Prostate Epithelial Cells

Abstract Objectives Selenoprotein F (SELENOF) levels are responsive to available dietary selenium and found in high levels in benign prostate cells. It is implicated in prostate cancer (PCa) mortality due to associations between polymorphisms in the corresponding gene and death from the disease. SELENOF levels are dramatically lower in prostate cancer compared to adjacent benign tissue. The objective of this study was to determine whether reducing SELENOF levels in human, non-transformed RWPE-1 prostate epithelial cells alters their phenotype to implicate SELENOF loss in PCa progression. Methods SELENOF levels were reduced in RWPE-1 cells that express high levels of SELENOF using a SELENOF shRNA construct. Proliferation was determined by quantifying DNA using fluorometric dsDNA quantitation. Growth in soft agar and cell mobility of cells in culture (wound healing assay) were imaged using an Evos FL microscope and quantified using Image J software. The oxygen consumption rate (OCR) was measured using a Seahorse XFe24 Analyzer. Results SELENOF levels were reduced in RWPE-1 and these cells exhibited decreased contact inhibition in culture (n = 3, P < 0.001) when compared to controls. Normal prostate epithelial cells are atypical in that they rely on glycolysis for energy production, have a truncated TCA cycle, and a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) occurs in PCa. Reducing SELENOF in RWPE-1 cells resulted in higher OCR compared to controls, indicating that SELENOF can impact the sources and pathways used in cellular energy metabolism. Conclusions Reduced SELENOF levels in RWPE-1 prostate cells resulted in properties consistent with a transformed phenotype and an increase in OCR, and indicating that the reduction in SELENOF may contribute a metabolic shift towards a PCa cancer-like metabolism. Together, these results indicate that SELENOF loss likely contributes to cancer progression. Funding Sources This work was supported by a grant from the Department of Defense to AMD and a Pre-Doctoral Education for Clinical and Translational Scientists Fellowship to LKH.

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