Abstract
The underlying molecular mechanism driving clear cell renal cell carcinoma (ccRCC) progression is still to be explored. The significant downregulation of protein tyrosine phosphatase nonreceptor type 3 (PTPN3) expression in the tumor tissues suggested its protective role in ccRCC progression. IHC analysis of PTPN3 protein in 172 ccRCC tissue revealed that PTPN3 was an independently favorable prognostic factor for progression-free survival (P = 0.0166) and overall survival (P = 0.0343) of patients. The ccRCC cell lines SN12C, 1932, ACHN, and Caki-1 were used to evaluate, both in vitro and in vivo, the biological roles of PTPN3. We observed that overexpression of PTPN3 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. In contrast, the knocking down of PTPN3 elicited opposite effects. Overexpressing PTPN3 inhibited xenograft tumor growth and lung metastasis displayed by the in vivo mice models. PTPN3 inhibited tumor cell motility by suppressing the phosphorylation of AKT, and subsequently inactivating the PI3K/AKT signaling pathway of renal cell carcinoma cells. Furthermore, the inhibition of phospho-AKTThr308 and phospho-AKTSer473 reversed PTPN3-induced silencing in tumor cell migration. Our work revealed that the overexpression of PTPN3 could suppress kidney cancer progression by negatively regulating the AKT signaling pathway, and served as a favorable prognostic factor in patients with ccRCC. Our findings provided insight that PTPN3 could be a potential target for therapy aiming to inhibit the malignant behaviors of ccRCC. IMPLICATIONS: PTPN3 is an independent favorable prognostic factor for patients with ccRCC and could be a potential target for therapy aiming to inhibit the malignant behaviors of ccRCC.
Highlights
Kidney cancer represents about 4% of all new cancer diagnoses [1]
Through the findings of various investigations, we reported that protein tyrosine phosphatase nonreceptor type 3 (PTPN3) could suppress clear cell renal cell carcinoma (ccRCC) progression by negatively regulating the AKT signaling pathway, providing insight that PTPN3 could be a potential target for therapy aiming to inhibit the malignant behaviors of ccRCC
Reduced expression of PTPN3 correlate with poor prognosis in patients with ccRCC
Summary
Kidney cancer represents about 4% of all new cancer diagnoses [1]. The most common form of kidney cancer arises from renal epithelium, termed as renal cell carcinoma As the most common histologic subtype, clear cell renal cell carcinoma (ccRCC) accounts for 70%–75% of all RCC cases [3]. The worldwide incidence and mortality rate of ccRCC has been estimated rising by 2%–3% per decade [4]. In spite of the fact that the small renal masses have been more frequently detected in recent year, one third of patients with ccRCC will suffer from metastatic diseases after the diagnosis [5].
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