TIP-B1 promotes kidney clear cell carcinoma growth and metastasis via EGFR/AKT signaling.

Lei Yin,Bo Peng,Heng Shi,Huan Yang,Keyi Wang,Shenglin Gao

doi:10.18632/aging.102298

Abstract

Kidney clear cell carcinoma (KIRC) is the most prevalent kidney malignancy. Accumulating evidence shows that high expression of TIP-B1 correlates with development of tumor progression. However, the detailed functions of TIP-B1 in the KIRC remain to be further elucidated. Here, we firstly found TIP-B1 expression was significantly increased in KIRC compared with adjacent normal tissues. What’s more, higher expression of TIP-B1 were correlated with aggressive clinico-pathological characteristics. In vitro assay found TIP-B1 knockdown dramatically inhibited KIRC cells proliferation, migration and invasion. In vivo assay found down regulated TIP-B1 could suppress tumor growth and metastasis. Mechanism analysis indicated that TIP-B1 could bind EGFR and suppress EGFR degradation, then promoted EGF-induced AKT signaling. Together, TIP-B1 could be applied as an independent risk factor to predict KIRC progression and metastasis. Targeting TIP-B1 might be a new potential therapeutic strategy for KIRC treatment.

Highlights

Renal cell carcinoma (RCC) is the most prevalent primary kidney malignancy and accounts for an estimated 90–95% of kidney cancer cases [1]
The detailed gene expression data were listed Supplementary Table 6. After merging those 3 datasets, 10 significantly upregulated genes both in tumor and metastasis tissues were identified (Figure 1A, Supplementary Table 6). We further validated those 10 genes in TCGA-Kidney clear cell carcinoma (KIRC) cohort and found only TIP-B1 expression was significantly correlative in receiver operating characteristics (ROC) curves associating with KIRC genesis (Figure 1F, Supplementary Figure 1), which suggested TIP-B1 might be a good indicator for KIRC
We analyzed the expression of TIP-B1 in TCGA-KIRC cohort and found that TIP-B1 expression was significantly upregulated in tumor tissues when compared with adjacent non-tumor kidney tissues (Figure 1C)

Summary

Introduction

Renal cell carcinoma (RCC) is the most prevalent primary kidney malignancy and accounts for an estimated 90–95% of kidney cancer cases [1]. Kidney clear cell carcinoma (KIRC) is the most prevalent subtype of RCC. Identifying prognostic biomarkers and therapeutic targets that contribute to the KIRC metastasis are extremely important. TIP-B1, a new gene which has been identified in 1999 [6], known as SH3BGRL3, belong to SH3BGR family [7]. Little is known about the role of TIP-B1 in tumors. Some studies reported TIP-B1 was detected www.aging-us.com in lung adenocarcinoma and bladder cancer patient urine [10, 11], which indicated TIP-B1 may play a key role in urothelial carcinoma. Whether TIP-B1 could promote KIRC growth and metastasis still need to be elucidated

Methods

Results

Conclusion