ArticleThe Journal of biological chemistry2014
Synergistic signaling of tumor cell invasiveness by hepatocyte growth factor and hypoxia.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- EBP1 promotes the malignant biological behaviors of kidney renal clear cell carcinoma through activation of p38/HIF-1α signaling pathway.Cancer cell international · 2024Article
- Breast cancer stem cells: mechanobiology reveals highly invasive cancer cell subpopulations.Cellular and molecular life sciences : CMLS · 2022Article
- Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines.Genes, chromosomes & cancer · 2021Article
- Autocrine signaling by receptor tyrosine kinases in urothelial carcinoma of the bladder.PloS one · 2021Article
- Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities.Nature reviews. Urology · 2019Review
- Article
- Hypoxia leads to decreased autophosphorylation of the MET receptor but promotes its resistance to tyrosine kinase inhibitors.Oncotarget · 2018Article
- Differential expression of DUSP2 in left- and right-sided colon cancer is associated with poor prognosis in colorectal cancer.Oncology letters · 2018Article
- Secretome analysis of breast cancer-associated adipose tissue to identify paracrine regulators of breast cancer growth.Oncotarget · 2017Article
- Choosing the right cell line for renal cell cancer research.Molecular cancer · 2016Review
- Article
- Molecular targets of luteolin in cancer.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2016Review
- Non-small-cell lung carcinoma: role of the Notch signaling pathway.Lung Cancer (Auckland, N.Z.) · 2015Review
- Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts.Drug design, development and therapy · 2014Article
- Inhibiting Autophagy in Renal Cell Cancer and the Associated Tumor Endothelium.Cancer journal (Sudbury, Mass.)Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocyte growth factor (HGF) signaling promotes tumor invasiveness in renal cell carcinoma (RCC) and other cancers. In clear cell RCC, VHL loss generates pseudohypoxia that exacerbates HGF-driven invasion through β-catenin deregulation. Hypoxia also enhances HGF-driven invasiveness by papillary RCC cells, but in the absence of VHL, loss signaling integration involves three parallel routes: 1) hypoxia-induced reactive oxygen species production and decreased DUSP2 expression, leading to enhanced mitogen-activated protein kinase (MAPK) cascade activation; 2) reactive oxygen species-induced diacylglycerol production by phospholipase Cγ, leading to protein kinase C activation and increased protein phosphatase- 2A activity, thereby suppressing HGF-induced Akt activation; and 3) a profound shift from HGF-enhanced, proliferation- oriented metabolism to autophagy-dependent invasion and suppression of proliferation. This tripartite signaling integration was not unique to RCC or HGF; in RCC cells, invasive synergy induced by the combination of hypoxia and epidermal growth factor occurred through the same mechanism, and in estrogen receptor-positive breast cancer cells, this mechanism was suppressed in the absence of estrogen. These results define the molecular basis of growth factor and hypoxia invasive synergy in VHL-competent papillary RCC cells, illustrate the plasticity of invasive and proliferative tumor cell states, and provide signaling profiles by which they may be predicted.
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