SPARC is a key mediator of TGF-β-induced renal cancer metastasis.
Ji-Ming BaoQiang DangChun-Jung LinU-Ging LoBoris FeldkorenAndrew DangElizabeth HernandezFei LiVandana PanwarCheng-Fan LeeJun-Jie CenBing GuanVitaly MargulisPayal KapurRolf A BrekkenJun-Hang LuoJer-Tsong HsiehWan-Long TanPublished in: Journal of cellular physiology (2020)
Aberrant expression of transforming growth factor-β1 (TGF-β1) is associated with renal cell carcinoma (RCC) progression by inducing cancer metastasis. However, the downstream effector(s) in TGF-β signaling pathway is not fully characterized. In the present study, the elevation of secreted protein acidic and rich in cysteine (SPARC) as a TGF-β regulated gene in RCC was identified by applying differentially expressed gene analysis and microarray analysis, we further confirmed this result in several RCC cell lines. Clinically, the expression of these two genes is positively correlated in RCC patient specimens. Furthermore, elevated SPARC expression is found in all the subtypes of RCC and positively correlated with the RCC stage and grade. In contrast, SPARC expression is inversely correlated with overall and disease-free survival of patients with RCC, suggesting SPARC as a potent prognostic marker of RCC patient survival. Knocking down SPARC significantly inhibits RCC cell invasion and metastasis both in vitro and in vivo. Similarly, in vitro cell invasion can be diminished by using a specific monoclonal antibody. Mechanistically, SPARC activates protein kinase B (AKT) pathway leading to elevated expression of matrix metalloproteinase-2 that can facilitate RCC invasion. Altogether, our data support that SPARC is a critical role of TGF-β signaling network underlying RCC progression and a potential therapeutic target as well as a prognostic marker.
Keyphrases
- renal cell carcinoma
- transforming growth factor
- poor prognosis
- epithelial mesenchymal transition
- signaling pathway
- free survival
- binding protein
- genome wide
- monoclonal antibody
- oxidative stress
- transcription factor
- case report
- computed tomography
- dendritic cells
- papillary thyroid
- machine learning
- dna methylation
- risk assessment
- squamous cell
- cell proliferation
- single molecule
- gene expression
- copy number
- amino acid
- electronic health record
- lymph node metastasis
- stress induced
- protein protein
- network analysis
- living cells
- ultrasound guided
- anti inflammatory