A-kinase-interacting protein 1 facilitates growth and metastasis of gastric cancer cells via Slug-induced epithelial-mesenchymal transition.

Dehu Chen,Gan Cao,Qinghong Liu

doi:10.1111/jcmm.14339

Dehu Chen, Gan Cao + Show 1 more

Open Access

https://doi.org/10.1111/jcmm.14339

Copy DOI

Abstract

A‐kinase‐interacting protein 1 (AKIP1) has previously been reported to act as a potential oncogenic protein in various cancers. The clinical significance and biological role of AKIP1 in gastric cancer (GC) is, however, still elusive. Herein, this study aimed to investigate the functional and molecular mechanism by which AKIP1 influences GC. AKIP1 mRNA and protein expressions in GC tissues were examined by quantitative real‐time PCR (qRT‐PCR), Western blot and immunohistochemistry. Other methods including stably transfected against AKIP1 into gastric cancer cells, wound healing, transwell assays, CCK‐8, colony formation, qRT‐PCR and Western blot in vitro and tumorigenesis in vivo were also performed. The up‐regulated expression of AKIP1 in GC specimens significantly correlated with clinical metastasis and poor prognosis in patients with GC. AKIP1 knockdown markedly suppressed GC cells proliferation, invasion and metastasis both in vitro and in vivo. In contrast, AKIP1 overexpression resulted in the opposite effects. Moreover, mechanistic analyses indicated that Slug‐induced epithelial‐mesenchymal transition (EMT) might be responsible for AKIP1‐influenced GC cells behaviour. Our findings demonstrated that high AKIP1 expression significantly correlated with clinical metastasis and unfavourable prognosis in patients with GC. Additionally, AKIP1 promoted GC cells proliferation, migration and invasion by activating Slug‐induced EMT.

Highlights

Gastric cancer (GC) is one of the most lethal malignancies worldwide.[1]
We demonstrated that A‐kinase‐interacting protein 1 (AKIP1) was highly ex‐ pressed in GC tissues compared with that in their non‐tu‐ mour counterparts
| 4441 overexpression of AKIP1 was positively correlated with tumour size, clinical metastasis, and a shorter OS time of GC patients, proving its crucial role in GC evolution and metastasis

Summary

| INTRODUCTION

Gastric cancer (GC) is one of the most lethal malignancies worldwide.[1]. Despite great improvements in surgical treatment and adjuvant ther‐ apy in recent decades, long‐term survival remains unsatisfactory on account of tumour recurrence and metastasis.[2,3] the inves‐ tigation of the molecular mechanisms underlying GC progression and metastasis contributes to identifying novel therapeutic targets, which is critical to improving GC treatment outcomes. Extensive evidence has demonstrated that epithelial‐ mesenchymal transition (EMT) functions importantly in the invasion and metastasis of various epithelial tumours.[4,5,6] The differentiation process that epithelial cells can down‐regulate epithelial properties and acquire mesenchymal features is commonly known as EMT. During this event, epithelial cells depolarize, lose their cell‐cell junc‐ tions and gain migratory and invasive potential, with the reduced expression of epithelial marker E‐cadherin and the increased ex‐ pression of mesenchymal marker N‐cadherin.[4] Regulation of EMT. We investigated the clinical signif‐ icance of AKIP1 in GC tissues, as well as the function and the underlying mechanism of AKIP1 in GC cells growth, migration and invasion

| MATERIALS AND METHODS

Findings

| DISCUSSION