HGF Mediates Cell Proliferation of Human Mesothelioma Cells through a PI3K/MEK5/Fra-1 Pathway

Ramos-Niño, Maria E.; Blumen, Steven R.; Sabo‐Attwood, Tara; Pass, Harvey I.; Carbone, Michele; Testa, Joseph R.; Altomare, Deborah A.; Mossman, Brooke T.

doi:10.1165/rcmb.2007-0206oc

Cited by 63 publications

(66 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A role for proliferation in PKD is supported by findings of increased BrdU incorporation (37), Ki-67 staining (38), and PCNA staining (39) in cyst-lining cells. Hyperactivation of c-Met would likely lead to increased proliferation (40,41), consistent with these findings. On the other hand, Piontek et al failed to find an increase in proliferation, and thus, the role of proliferation in PKD remains controversial (42).…”

Section: Discussionsupporting

confidence: 76%

Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease

Qin¹,

Taglienti²,

Nauli³

et al. 2010

J. Clin. Invest.

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder that is caused by mutations at two loci, polycystin 1 (PKD1) and polycystin 2 (PKD2). It is characterized by the formation of multiple cysts in the kidneys that can lead to chronic renal failure. Previous studies have suggested a role for hyperactivation of mammalian target of rapamycin (mTOR) in cystogenesis, but the etiology of mTOR hyperactivation has not been fully elucidated. In this report we have shown that mTOR is hyperactivated in Pkd1-null mouse cells due to failure of the HGF receptor c-Met to be properly ubiquitinated and subsequently degraded after stimulation by HGF. In Pkd1-null cells, Casitas B-lineage lymphoma (c-Cbl), an E3-ubiquitin ligase for c-Met, was sequestered in the Golgi apparatus with α 3 β 1 integrin, resulting in the inability to ubiquitinate c-Met. Treatment of mouse Pkd1-null cystic kidneys in organ culture with a c-Met pharmacological inhibitor resulted in inhibition of mTOR activity and blocked cystogenesis in this mouse model of ADPKD. We therefore suggest that blockade of c-Met is a potential novel therapeutic approach to the treatment of ADPKD.

show abstract

Section: Discussionsupporting

confidence: 76%

Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease

Qin¹,

Taglienti²,

Nauli³

et al. 2010

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The transcription factor activator protein-1, which is a target of asbestos-induced signalling pathways, was also shown to be critical to the transformation of mesothelial cells through ERK-dependent Fos-related antigen (Fra)-1 elevation [87]. Hepatocyte growth factor (HGF)/scatter factor and its receptor tyrosine kinase, c-Met, are highly expressed in most human malignant mesotheliomas and recently, it was shown that HGF-mediated cell proliferation of human mesothelioma cells through a phosphoinositide 3-kinase (PI3K)/MAP kinase 5/Fra-1 pathway [88]. Moreover, c-Met was shown to be a relevant experimental treatment target as well as a negative prognostic factor [89,90].…”

Section: Figurementioning

confidence: 99%

Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

2015

View full text Add to dashboard Cite

Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society. @ERSpublications Malignant pleural mesothelioma is a cancer with increasing death tolls due to the past and present use of asbestos http://ow.ly/DhA2y

show abstract

“…HGF/c-Met has been proved to be involved in the progression of many malignancies and the spread of disease (26)(27)(28)(29). in MM patients, elevated levels of HGF have been found in serum and BM, compared to healthy controls (30)(31)(32)(33), indicating that a high serum level of HGF at the time of diagnosis has a strong negative prognostic impact (30,33).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of c-Met inhibits cell proliferation and invasion and increases chemosensitivity to doxorubicin in human multiple myeloma U266 cells in vitro

Que

Chen

2011

Mol Med Rep

View full text Add to dashboard Cite

Abstract. c-Met, a receptor tyrosine kinase and its ligand, hepatocyte growth factor, are critical in cellular proliferation, motility and invasion and confer resistance to specific chemotherapeutic drugs. However, little is known about the impact of c-Met knockdown on the biological functions of human multiple myeloma u266 cells. The present study was designed to determine the role of c-Met in the proliferation and invasion of u266 cells, using rna interference technology in vitro. in our study, the c-Met short hairpin rna (shrna) was successfully transfected into u266 cells, which resulted in the significant inhibition of transcription and expression of c-Met. The down-regulation of c-Met inhibited the proliferation potential, adherence and invasiveness of u266 cells, and also increased chemosensitivity to doxorubicin. The c-Met shRNA in u266 cells induced apoptosis and increased the accumulation of cleavage ParP and cleavage caspase-3. However, the expression of Bcl-2 and Bax did not change following the c-Met knockdown. Taken together, our data reveal that the down-regulation of c-Met inhibits proliferation and invasion and increases the chemosensitivity of u266 cells. Thus, the targeting of c-Met could be an effective therapeutic approach against multiple myeloma. IntroductionMultiple myeloma (MM) is the second most common hematological malignancy, characterized by the clonal proliferation of neoplastic plasma cells in the bone marrow (BM). At present, MM is an incurable disease, in spite of the fact that most patients to a certain extent respond to chemotherapy. High-dose chemotherapy with stem cell support has achieved higher response rates than conventional therapies, but few patients remain in long-term remission. new effective anticancer targets for both early and advanced MM is a dynamic research area (1-5).The interaction of MM cells with extracellular matrix (ECM) proteins and BM cells, as well as factors in the BM milieu (cytokines, chemokines and angiogenesis), play a crucial role in MM pathogenesis (6-9). The interaction of MM cells with the BM microenvironment activates MM cell proliferation and the anti-apoptotic signaling cascades (10,11). These molecular events are triggered directly, via cell adhesion molecule-mediated interactions, or indirectly by growth factors released by BM stromal cells (BMSCs), MM cells or both (12,13).Hepatocyte growth factor (HGF) is a multifunctional protein. c-Met is the receptor for HGF, a protein product of a proto-oncogene (14). it is a transmembrane tyrosine kinase with structural and functional features of a growth factor receptor (15). on binding with its ligand, autophosphorylation of the receptor stimulates its intrinsic tyrosine kinase activity with resultant changes in cellular motility, growth and invasion. c-Met overexpression has been found in numerous human tumors (16,17). Previous studies have revealed that c-Met and its ligand HGF are overexpressed in human myeloma cell lines (JJn-3, u-266, oH-2 and JW) and primary human MM cells (18). in addition,...

show abstract

HGF Mediates Cell Proliferation of Human Mesothelioma Cells through a PI3K/MEK5/Fra-1 Pathway

Cited by 63 publications

References 32 publications

Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease

Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease

Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

Knockdown of c-Met inhibits cell proliferation and invasion and increases chemosensitivity to doxorubicin in human multiple myeloma U266 cells in vitro

Contact Info

Product

Resources

About