Overexpression of SATB1 is associated with biologic behavior in human renal cell carcinoma.

Chao Cheng,Fuqing Zeng,Lian Liu,Feng Wan,Xuepan Chen,Xiaofei Wu,Shi'An Xing,Zhaohui Zhu,Neil A Bhowmick

doi:10.1371/journal.pone.0097406

Abstract

Special AT-rich sequence-binding protein-1 (SATB1) has been reported to be aberrantly expressed in various cancers and correlated with the malignant behavior of cancer cells. However, the function of SATB1 in RCC remains unclear. With the combination of immunohistochemistry, western blotting, immunofluorescence, qRT-PCR, and cell proliferation, migration and invasion assays, we found that levels of SATB1 mRNA and protein were dramatically increased in human ccRCC tissues (P<0.001 for both), and upregulation of SATB1 was significantly associated with depth of invasion (P<0.001), lymph node status (P = 0.001) and TNM stage (P = 0.009). SATB1 knockdown inhibited the proliferation, migration and invasion of 786-O cells, whereas SATB1 overexpression promoted the growth and aggressive phenotype of ACHN cells in vitro. Furthermore, SATB1 expression was positively correlated with ZEB2 expression (P = 0.013), and inversely linked to levels of SATB2 and E-cadherin (P = 0.005 and P<0.001, respectively) in ccRCC tissues. Our data provide a basis for the concept that overexpression of SATB1 may play a critical role in the acquisition of an aggressive phenotype for RCC cells through EMT, providing new insights into the significance of SATB1 in invasion and metastasis of ccRCC, which may contribute to fully elucidating the exact mechanism of development and progression of RCC.

Highlights

Renal cell carcinoma (RCC) is the most prevalent malignancy of the adult kidney, accounting for approximately 90–95% of all kidney neoplasms [1]
To further confirm these observations, we investigated the expression of Special AT-rich binding protein 1 (SATB1) in clear cell renal cell carcinoma (ccRCC) tissues and paired tissues using western blotting
We found that SATB1 and ZEB2 levels were significantly up-regulated in ccRCC tissues as compared with those in the paired normal tissues, whereas the expressions of SATB2 and E-cadherin were remarkably decreased in cancer tissues (Fig. 5)

Summary

Introduction

Renal cell carcinoma (RCC) is the most prevalent malignancy of the adult kidney, accounting for approximately 90–95% of all kidney neoplasms [1]. The clear cell renal cell carcinoma (ccRCC) is the most common histopathological subtype, comprising 70–80% of all RCCs [4]. Considerable improvements have been made in diagnosis, surgical techniques and adjuvant therapies in last decades, patients with ccRCC still face a dismal clinical outcome owing to high rate of metastasis both at initial presentation and after radical nephrectomy [2,5,6,7]. The overall five-year survival rate of patient with RCC ranges from 5% to 10%, with a median survival of only about 13 months [8,9]. Identification of novel biomarkers associated with disease progression and metastasis of RCC and combination of their application with traditional diagnostic and prognostic parameters would contribute to development of effective strategies for the prevention, early diagnosis and treatment of RCC

Methods

Results

Conclusion