scholarly journals Prostate tumor progression is mediated by a paracrine TGF-β/Wnt3a signaling axis

Oncogene ◽  
2008 ◽  
Vol 27 (56) ◽  
pp. 7118-7130 ◽  
Author(s):  
X Li ◽  
V Placencio ◽  
J M Iturregui ◽  
C Uwamariya ◽  
A-R Sharif-Afshar ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Prostate Tumor ◽  
Signaling Axis

scholarly journals Rad9 Protein Contributes to Prostate Tumor Progression by Promoting Cell Migration and Anoikis Resistance

2012 ◽  
Vol 287 (49) ◽  
pp. 41324-41333 ◽  
Author(s):  
Constantinos G. Broustas ◽  
Aiping Zhu ◽  
Howard B. Lieberman
Keyword(s):  
Cell Migration ◽  
Tumor Progression ◽  
Prostate Tumor ◽  
Anoikis Resistance

The secreted matrix protein mindin increases prostate tumor progression and tumor-bone crosstalk via ERK 1/2 regulation

2019 ◽  
Vol 40 (7) ◽  
pp. 828-839
Author(s):  
Juan A Ardura ◽  
Irene Gutiérrez-Rojas ◽  
Luis Álvarez-Carrión ◽  
M Rosario Rodríguez-Ramos ◽  
José M Pozuelo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Matrix Protein ◽  
Bone Cells ◽  
Prostate Tumor ◽  
Dependent Manner ◽  
Prostate Tumors ◽  
Adenocarcinoma Cells ◽  
Prostate Tumor Cells

Abstract Advanced prostate cancer cells preferentially metastasize to bone by acquiring a bone phenotype that allows metastatic cells to thrive in the skeletal environment. Identification of factors that promote the expression of ectopic bone genes—process known as osteomimicry—leading to tumor progression is crucial to prevent and treat metastatic prostate cancer and prolong life expectancy for patients. Here, we identify the extracelular matrix protein mindin in the secretome of prostate adenocarcinoma cells and show that mindin overexpression in human and mouse TRAMP-C1-induced prostate tumors correlates with upregulated levels of bone-related genes in the tumorigenic prostate tissues. Moreover, mindin silencing decreased osteomimicry in adenocarcinoma cells and in the prostate tumor mice model, as well as reduced tumor cell proliferation, migration and adhesion to bone cells. Inhibition of the extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation decreased the proliferative, migratory and pro-adhesion actions of mindin on prostate tumor cells. In addition, conditioned media obtained by crosstalk stimulation of either osteocytes or osteoblasts with the secretome of TRAMP-C1 cells promoted osteomimicry in prostate tumor cells; an effect inhibited by mindin silencing of TRAMP-C1 cells. In vivo, tibiae of primary tumor-bearing mice overexpressed the pro-angiogenic and pro-metastattic factor vascular endothelial growth factor receptor 2 (VEGFR2) in a mindin-dependent manner. Our findings indicate that mindin is a novel regulator of osteomimicry in prostate tumors and potentially mediates tumor-bone cell crosstalk, suggesting its promising role as a target to inhibit bone metastases.

scholarly journals E2f binding-deficient Rb1 protein suppresses prostate tumor progression in vivo

2010 ◽  
Vol 108 (2) ◽  
pp. 704-709 ◽  
Author(s):  
H. Sun ◽  
Y. Wang ◽  
M. Chinnam ◽  
X. Zhang ◽  
S. W. Hayward ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Prostate Tumor

scholarly journals A Stromal Lysolipid–Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression

2019 ◽  
Vol 9 (5) ◽  
pp. 617-627 ◽  
Author(s):  
Francesca R. Auciello ◽  
Vinay Bulusu ◽  
Chet Oon ◽  
Jacqueline Tait-Mulder ◽  
Mark Berry ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pancreatic Tumor ◽  
Signaling Axis

scholarly journals Role of Calcium Signaling in Prostate Cancer Progression: Effects on Cancer Hallmarks and Bone Metastatic Mechanisms

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1071 ◽  
Author(s):  
Juan A. Ardura ◽  
Luis Álvarez-Carrión ◽  
Irene Gutiérrez-Rojas ◽  
Verónica Alonso
Keyword(s):  
Prostate Cancer ◽  
Calcium Channels ◽  
Calcium Signaling ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Transient Receptor Potential ◽  
Prostate Tumor ◽  
Tumor Cell Death ◽  
Prostate Cancers

Advanced prostate cancers that progress to tumor metastases are often considered incurable or difficult to treat. The etiology of prostate cancers is multi-factorial. Among other factors, de-regulation of calcium signals in prostate tumor cells mediates several pathological dysfunctions associated with tumor progression. Calcium plays a relevant role on tumor cell death, proliferation, motility-invasion and tumor metastasis. Calcium controls molecular factors and signaling pathways involved in the development of prostate cancer and its progression. Such factors and pathways include calcium channels and calcium-binding proteins. Nevertheless, the involvement of calcium signaling on prostate cancer predisposition for bone tropism has been relatively unexplored. In this regard, a diversity of mechanisms triggers transient accumulation of intracellular calcium in prostate cancer cells, potentially favoring bone metastases development. New therapies for the treatment of prostate cancer include compounds characterized by potent and specific actions that target calcium channels/transporters or pumps. These novel drugs for prostate cancer treatment encompass calcium-ATPase inhibitors, voltage-gated calcium channel inhibitors, transient receptor potential (TRP) channel regulators or Orai inhibitors. This review details the latest results that have evaluated the relationship between calcium signaling and progression of prostate cancer, as well as potential therapies aiming to modulate calcium signaling in prostate tumor progression.

scholarly journals Abi1 loss drives prostate tumorigenesis through activation of EMT and non-canonical WNT signaling

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Disharee Nath ◽  
Xiang Li ◽  
Claudia Mondragon ◽  
Dawn Post ◽  
Ming Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Wnt Signaling ◽  
Tumor Progression ◽  
Cell Line ◽  
Rna Sequencing ◽  
Cell Lines ◽  
Adaptor Protein ◽  
Prostate Tumor ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Abstract Background Prostate cancer development involves various mechanisms, which are poorly understood but pointing to epithelial mesenchymal transition (EMT) as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, acts as tumor suppressor in prostate cancer but the role of ABI1 in EMT is not clear. Methods To investigate the molecular mechanism by which loss of ABI1 contributes to tumor progression, we disrupted the ABI1 gene in the benign prostate epithelial RWPE-1 cell line and determined its phenotype. Levels of ABI1 expression in prostate organoid tumor cell lines was evaluated by Western blotting and RNA sequencing. ABI1 expression and its association with prostate tumor grade was evaluated in a TMA cohort of 505 patients and metastatic cell lines. Results Low ABI1 expression is associated with biochemical recurrence, metastasis and death (p = 0.038). Moreover, ABI1 expression was significantly decreased in Gleason pattern 5 vs. pattern 4 (p = 0.0025) and 3 (p = 0.0012), indicating an association between low ABI1 expression and highly invasive prostate tumors. Disruption of ABI1 gene in RWPE-1 cell line resulted in gain of an invasive phenotype, which was characterized by a loss of cell-cell adhesion markers and increased migratory ability of RWPE-1 spheroids. Through RNA sequencing and protein expression analysis, we discovered that ABI1 loss leads to activation of non-canonical WNT signaling and EMT pathways, which are rescued by re-expression of ABI1. Furthermore, an increase in STAT3 phosphorylation upon ABI1 inactivation and the evidence of a high-affinity interaction between the FYN SH2 domain and ABI1 pY421 support a model in which ABI1 acts as a gatekeeper of non-canonical WNT-EMT pathway activation downstream of the FZD2 receptor. Conclusions ABI1 controls prostate tumor progression and epithelial plasticity through regulation of EMT-WNT pathway. Here we discovered that ABI1 inhibits EMT through suppressing FYN-STAT3 activation downstream from non-canonical WNT signaling thus providing a novel mechanism of prostate tumor suppression.

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