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SPARC is a key mediator of TGF‐β‐induced renal cancer metastasis
Author(s) -
Bao JiMing,
Dang Qiang,
Lin ChunJung,
Lo UGing,
Feldkoren Boris,
Dang Andrew,
Hernandez Elizabeth,
Li Fei,
Panwar Vandana,
Lee ChengFan,
Cen JunJie,
Guan Bing,
Margulis Vitaly,
Kapur Payal,
Brekken Rolf A.,
Luo JunHang,
Hsieh JerTsong,
Tan WanLong
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29975
Subject(s) - cancer research , metastasis , renal cell carcinoma , biology , transforming growth factor , signal transduction , tumor progression , cancer , tissue microarray , protein kinase b , medicine , pathology , microbiology and biotechnology , genetics
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.