scholarly journals Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition

Oncogene ◽  
2012 ◽  
Vol 32 (2) ◽  
pp. 141-150 ◽  
Author(s):  
S K Gupta ◽  
S Oommen ◽  
M-C Aubry ◽  
B P Williams ◽  
N E Vlahakis
Keyword(s):  
Tumor Growth ◽  
Malignant Tumor ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis

scholarly journals Nicotinic Acetylcholine Receptor Signaling in Tumor Growth and Metastasis

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Sandeep Singh ◽  
Smitha Pillai ◽  
Srikumar Chellappan
Keyword(s):  
Tumor Growth ◽  
Nicotinic Acetylcholine Receptors ◽  
Tobacco Smoke ◽  
Acetylcholine Receptors ◽  
Epithelial Mesenchymal Transition ◽  
Antitumor Effects ◽  
Nicotinic Acetylcholine ◽  
Mesenchymal Transition ◽  
Promote Cell Proliferation ◽  
Tumor Growth And Metastasis

Cigarette smoking is highly correlated with the onset of a variety of human cancers, and continued smoking is known to abrogate the beneficial effects of cancer therapy. While tobacco smoke contains hundreds of molecules that are known carcinogens, nicotine, the main addictive component of tobacco smoke, is not carcinogenic. At the same time, nicotine has been shown to promote cell proliferation, angiogenesis, and epithelial-mesenchymal transition, leading to enhanced tumor growth and metastasis. These effects of nicotine are mediated through the nicotinic acetylcholine receptors that are expressed on a variety of neuronal and nonneuronal cells. Specific signal transduction cascades that emanate from different nAChR subunits or subunit combinations facilitate the proliferative and prosurvival functions of nicotine. Nicotinic acetylcholine receptors appear to stimulate many downstream signaling cascades induced by growth factors and mitogens. It has been suggested that antagonists of nAChR signaling might have antitumor effects and might open new avenues for combating tobacco-related cancer. This paper examines the historical data connecting nicotine tumor progression and the recent efforts to target the nicotinic acetylcholine receptors to combat cancer.

scholarly journals MicroRNA-150 suppresses epithelial-mesenchymal transition, invasion, and metastasis in prostate cancer through the TRPM4-mediated β-catenin signaling pathway

2019 ◽  
Vol 316 (4) ◽  
pp. C463-C480 ◽  
Author(s):  
Xi Hong ◽  
Jian-Jun Yu
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Transient Receptor Potential ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Transient Receptor Potential Melastatin ◽  
Tumor Growth And Metastasis

Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths among males. The aim of the current study was to investigate the ability of microRNA-150 (miR-150) targeting transient receptor potential melastatin 4 (TRPM4) to mediate epithelial-mesenchymal transition (EMT), invasion, and metastasis through the β-catenin signaling pathway in PCa. Microarray analysis was performed to identify PCa-related differentially expressed genes, after which both the mirDIP and TargetScan databases were employed in the prediction of the miRNAs regulating TRPM4. Immunohistochemistry and RT-qPCR were conducted to determine the expression pattern of miR-150 and TRPM4 in PCa. The relationship between miR-150 and TRPM4 expression was identified. By perturbing miR-150 and TRPM4 expression in PCa cells, cell proliferation, migration, invasion, cycle, and apoptosis as well as EMT markers were determined accordingly. Finally, tumor growth and metastasis were evaluated among nude mice. Higher TRPM4 expression and lower miR-150 expression and activation of the β-catenin signaling pathway as well as EMT stimulation were detected in the PCa tissues. Our results confirmed TRPM4 as a target of miR-150. Upregulation of miR-150 resulted in inactivation of the β-catenin signaling pathway. Furthermore, the upregulation of miR-150 or knockdown of TRPM4 was observed to suppress EMT, proliferation, migration, and invasion in vitro in addition to restrained tumor growth and metastasis in vivo. The evidence provided by our study highlights the involvement of miR-150 in the translational suppression of TRPM4 and the blockade of the β-catenin signaling pathway, resulting in the inhibition of PCa progression.

scholarly journals Cancer-associated fibroblast secretion of PDGFC promotes gastrointestinal stromal tumor growth and metastasis

Oncogene ◽  
2021 ◽  
Vol 40 (11) ◽  
pp. 1957-1973
Author(s):  
Hyunho Yoon ◽  
Chih-Min Tang ◽  
Sudeep Banerjee ◽  
Mayra Yebra ◽  
Sangkyu Noh ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tumor Growth ◽  
Gastrointestinal Stromal Tumor ◽  
Single Agent ◽  
Stromal Tumor ◽  
Paracrine Signaling ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis ◽  
Factor C

AbstractTargeted therapies for gastrointestinal stromal tumor (GIST) are modestly effective, but GIST cannot be cured with single agent tyrosine kinase inhibitors. In this study, we sought to identify new therapeutic targets in GIST by investigating the tumor microenvironment. Here, we identified a paracrine signaling network by which cancer-associated fibroblasts (CAFs) drive GIST growth and metastasis. Specifically, CAFs isolated from human tumors were found to produce high levels of platelet-derived growth factor C (PDGFC), which activated PDGFC-PDGFRA signal transduction in GIST cells that regulated the expression of SLUG, an epithelial-mesenchymal transition (EMT) transcription factor and downstream target of PDGFRA signaling. Together, this paracrine induce signal transduction cascade promoted tumor growth and metastasis in vivo. Moreover, in metastatic GIST patients, SLUG expression positively correlated with tumor size and mitotic index. Given that CAF paracrine signaling modulated GIST biology, we directly targeted CAFs with a dual PI3K/mTOR inhibitor, which synergized with imatinib to increase tumor cell killing and in vivo disease response. Taken together, we identified a previously unappreciated cellular target for GIST therapy in order to improve disease control and cure rates.

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