Overexpression of SATB1 Is Associated with Biologic Behavior in Human Renal Cell Carcinoma

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.

Pilot study special AT-rich sequence-binding protein 1 investigating as a potential biomarker for esophageal squamous cell carcinoma

“…14 SATB1 binds to specific nuclear matrix attachment regions of the DNA and regulates genes involved in a variety of important biological process, involving rapid growth, differentiation, apoptosis, DNA recovery, transcription, and expression profile reprogramming. 15 Recently, SATB1 expression has been shown to correlate with unfavorable tumor characteristics in various types of cancer by promoting enhanced tumor growth and malignant metastasis. [16][17][18] Limited data are available regarding the influence of SATB1 expression on ESCC growth and progression.…”

SATB1 expression is correlated with β-catenin associated epithelial–mesenchymal transition in colorectal cancer

“…This phenomenon has also been reported in other types of tumors, such as liver, prostate, ovarian, gastric, and kidney tumors. [8][9][10][11][12] We further analyzed the expression of SATB1 in corresponding lymph node metastases, and we found that SATB1 expression was remarkably higher in lymph node metastases than in CRC primary lesions. These results suggest that SATB1 plays a crucial role in promoting tumor growth, invasion, and metastasis.…”

“…7 It has subsequently been found to correlate with poor prognosis in several other forms of tumor, such as liver cancer, 8 prostate cancer, 9 ovarian cancer, 10 gastric cancer, 11 and renal cell carcinoma. 12 As such, SATB1 is considered to be a new type of key oncogene regulator. In several current investigations of SATB1 expression in CRC, the data showed that high expression of SATB1 promotes the growth and metastasis of CRC.…”

Genetic variants in chromatin-remodeling pathway associated with lung cancer risk in a Chinese population

“…SATB1 was overexpressed in bladder cancer cells and regulated the growth and apoptosis of malignant cell (Han et al, 2013). Recently, several studies demonstrated that high expression level of SATB1 correlated with advanced stages of cancers including colon cancer, liver cancer, prostate cancer and renal cell carcinoma (Cheng et al, 2014;Shukla et al, 2013;Tu et al, 2012;Fromberg et al, 2014). The rs6808523 variant is located at the first intron of SATB1.…”

“…To validate this hypothesis, we systematically selected six key genes (SMARCA5, SMARCC2, SMARCD2, ARID1A, NR3C1 and SATB1) in chromatin remodeling pathway, which had been reported associated with cancer in previous studies (Jin et al, 2014;Kim et al, 2013;Cruickshank et al, 2015;Han et al, 2015;Pan et al, 2011;Cheng et al, 2014), and evaluated the association of these genetic variants and lung cancer risk with a case-control design including 1341 cases and 1982 controls.…”