Expression and clinical value of SALL4 in renal cell carcinomas

Abstract

The aim of the present study was to investigate the expression of spalt like transcription factor 4 (SALL4) in the three most common types of renal cell carcinomas (rcc) [clear cell rcc (ccrcc), papillary renal cell carcinoma (prcc) and chromophobe rcc (chrcc)], and the association with the overall survival (oS) of patients. The cancer Genome atlas (TcGa) database and rcc samples were used to investigate the expression levels of the SALL4 gene and its association with the oS in the three types of rcc based on the analysis of the transcriptome, copy number and survival data. it was found that Sall4 was highly expressed in ccrcc and prcc tumor tissue, and low mrna expression level of SALL4 indicated a prolonged survival in both ccrcc and prcc. This mrna expression level was associated with pathological Tumor-node-Metastasis stage, M and T stages in both ccrcc and prcc. The analysis of the enriched pathway results suggested that Sall4 may act via translation initiation, and that the related genes promoted the progression of rcc. Moreover, the high expression level of Sall4 was detected in rcc samples and serum from patients. it was demonstrated that Sall4 promotes increased viability in rcc cells. Therefore, the present results suggest that Sall4 may be a sensitive and specific cancer biomarker in ccRCC and prcc. Furthermore, targeting of Sall4 may improve rcc therapy and prolong the survival of patients with ccrcc or prcc.

The new advance of SALL4 in cancer: Function, regulation, and implication

“…SALL4 downregulation inhibits endothelial cell proliferation, cell cycle progression, migration, and tube formation through the modulation of HIF‐1α/VEGF signaling, PI3K/Akt, and Wnt/β‐catenin pathways in the human umbilical vein endothelial cells (HUVEC) 61 . Additionally, VHL mutation‐mediated SALL4 overexpression promotes clear cell renal cell carcinoma (ccRCC) cell proliferation, colony formation, cell cycle progression, migration, invasion, tumorigenicity, and tumor vascularization through modulating Akt/GSK‐3β axis and vascular endothelial growth factor A (VEGFA) expression and inhibiting cell senescence 62,63 . Taken together, SALL4‐mediated angiogenesis is essential for cancer development and could be developed as a novel target for cancer therapy.…”

“…61 Additionally, VHL mutation-mediated SALL4 overexpression promotes clear cell renal cell carcinoma (ccRCC) cell proliferation, colony formation, cell cycle progression, migration, invasion, tumorigenicity, and tumor vascularization through modulating Akt/GSK-3β axis and vascular endothelial growth factor A (VEGFA) expression and inhibiting cell senescence. 62,63 Taken together, SALL4-mediated angiogenesis is essential for cancer development and could be developed as a novel target for cancer therapy.…”

Hypoxia increases RCC stem cell phenotype via altering the androgen receptor (AR)-lncTCFL5-2-YBX1-SOX2 signaling axis

“…The majority of RCC is of the clear cell type RCC (ccRCC) that has a gender bias in incidence with male to female ratio of 2.3:1, suggesting that AR signals might play promotional roles for the RCC development and progression [ 5 ]. He et al found that AR could promote RCC development and tumor metastasis via studies using various in vitro cell lines and in vivo mice models [ 6 ].…”

Co-overexpression of self-renewal markers SALL4 and HIWI is correlated with depth of tumor invasion and metastasis in colorectal cancer

“…The zinc finger transcription factor Sal-like protein 4 (SALL4) maintains pluripotency and self-renewal capacities of embryonic stem cells (ESCs) [6]. It was firstly cloned based on its sequence homology to Drosophila spalt gene [7][8][9].…”

“…Subsequently, SALL4 expression was reported in different malignancies including germ cell tumors [11,12], glioma [13], sharp myeloid leukemia [14], as well as breast [15], colorectal [16], lung [17], and liver [18] cancers. Furthermore, SALL4 communicates with the Wnt/β-catenin pathway as one of the major cell signaling pathways [14] to advance cell growth and cancer development [6,19]. PIWI-like RNA-mediated gene silencing 1 (PIWIL1), also called HIWI, is an evolutionarily conserved member of the PIWI subfamily of Argonaut proteins involved in stem cell self-renewal, RNA silencing, and regulation of translation.…”