Tumor Protein D52 (TPD52) Inhibits Growth and Metastasis in Renal Cell Carcinoma Cells Through the PI3K/Akt Signaling Pathway

Abstract

Tumor protein D52 (TPD52) is a member of the TPD52-like protein family and plays different roles in various types of malignancies. However, its role in renal cell carcinoma (RCC) is still unclear. In this study, we investigated the role of TPD52 in RCC. The mechanism of TPD52 in RCC was also investigated. Our data demonstrated that the expression levels of TPD52 in both mRNA and protein were significantly decreased in RCC cells. Overexpression of TPD52 inhibited proliferation, migration, and invasion with decreased epithelial-mesenchymal transition (EMT) phenotype in RCC cells, as well as attenuated tumor growth in renal cancer xenografts. Mechanistically, overexpression of TPD52 significantly inhibited downregulated phosphorylation levels of PI3K and Akt in RCC cells. In conclusion, the present study demonstrated that TPD52 inhibited growth and metastasis of RCC, at least in part, by suppressing the PI3K/Akt signaling pathway. Therefore, these findings suggest that TPD52 may be a promising therapeutic target for the treatment of human RCC.

<p>Knockdown of lncRNA <em>PCAT6</em> Enhances Radiosensitivity in Triple-Negative Breast Cancer Cells by Regulating<em> miR-185-5p</em>/<em>TPD52</em> Axis</p>

“…Moreover, accumulating evidence revealed that TPD52 was involved in cellular transformation, proliferation, apoptosis, and metastasis. 40,41 Yang et al demonstrated that knockdown of TPD52L2 (a member of the TPD52) suppressed the proliferation and colony formation in BC cells. 42 Zhang et al found that TPD52 expression was markedly increased in BC tissues and cells, and deficiency of miR-449 promoted proliferation and metastasis of BC cells through regulating TPD52.…”

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

“…To a further extent, PI3K/AKT/mTOR is identified as a highly enriched pathway in translocation RCC with TFE3 fusion (TFE3-tRCC) by miRNA microarray analysis [258]. Besides that PIK3R1 regulates EMT and stem-like phenotype of RCC cells through the AKT/GSK3β/CTNNB1 pathway [259], FoxO, PKCε, TPD52, NOTCH1, ETS2, miR-19b, -122, -182, -193a-3p, -195, and -224, as well as LncRNA MALAT1, TP73-AS1 and HOTTIP modulate proliferation, apoptosis, invasion, metastasis, or EMT via PI3K/ AKT pathway [260][261][262][263][264][265][266][267][268][269][270][271][272]. However, only a few of clinical trials of PI3K/AKT inhibitors in touch try to offer hope for KC patients (Tables 2 and 3).…”

Expression of tumor growth related genes in IRE1 knockdown U87 glioma cells: effect of hypoxia

“…1). Thus, strong up-regulation was shown for BRCA1 and TPD52 genes, both of which act as tumor suppressors [21,24]. Moreover, BRCA1 participates in maintaining genomic stability, in ubiquitination of specific proteins and transcriptional regulation [21].…”

“…Moreover, BRCA1 participates in maintaining genomic stability, in ubiquitination of specific proteins and transcriptional regulation [21]. Tumor protein D52 inhibits growth and metastasis of renal cell carcinoma through the PI3K/ AKT signaling pathway since plays different roles in various types of malignancies [24]. Thus, our results concerning up-regulation of BRCA1 and TPD52 gene expressions in IRE1 knockdown cells agree well with the functional role of BRCA1 and TPD52 proteins and also with suppression of glioma cell proliferation after inhibition of IRE1 [4,21,24,28].…”

“…Tumor protein D52 (TPD52) plays diffe rent roles in various types of malignancies. But in renal cell carcinoma it inhibits growth and metastasis through the PI3K/AKT signaling pathway [24]. Protein DEK induced cell proliferation through upregulating cell cycle related CDK signaling and promoted cell migration, and thus its expression is required for tumorigenesis and metastasis [25].…”