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. 2020 Oct 21;24(5):253-259.
doi: 10.1080/19768354.2020.1833985.

Aquaporin-1 facilitates proliferation and invasion of gastric cancer cells via GRB7-mediated ERK and Ras activation

Zhenjie Wang  1 , Yujuan Wang  2 , Yuan He  3 , Ning Zhang  1 , Wei Chang  4 , Yahui Niu  1
Affiliations

Aquaporin-1 facilitates proliferation and invasion of gastric cancer cells via GRB7-mediated ERK and Ras activation

Zhenjie Wang et al. Anim Cells Syst (Seoul). .

Abstract

Gastric cancer, one of the most common malignant tumors of the digestive tract, is devoid of effective treatment owing to its highly invasive ability. Aquaporins (AQPs), transmembrane water channel proteins, has been shown to be involved in the malignancy of gastric cancer. This study aims to investigate the pathophysiological roles of AQP-1 in gastric cancer. We first demonstrated quantitative real-time polymerase chain reaction analysis and found up-regulation of AQP-1 in gastric cancer cell lines. Additionally, silence of AQP-1 inhibited cell proliferation via decrease of proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2). Moreover, migration and invasion of gastric cancer cells were also suppressed by the interference of AQP-1. However, the tumorigenic mechanism of AQP-1 on gastric cancer is yet to be found. We demonstrated western blot analysis and found that knockdown of AQP-1 decreased protein expression of phospho (p)-GRB7 (growth factor receptor-bound protein 7) and led to a remarkable reduction of p-extracellular signal-regulated kinase (ERK) via inactivation of RAS. In general, our findings indicated that AQP-1 facilitates proliferation and invasion of gastric cancer cells via GRB7-mediated ERK and Ras activation, illuminating a novel AQP-1-RAS/ERK molecular axis as regulator in gastric cancer progression and suggesting potential implications in the treatment of gastric cancer.

Keywords: AQP-1; ERK; GRB7; RAS; gastric cancer.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Up-regulation of AQP-1 in gastric cancer cell lines. The expression of AQP-1 in gastric cancer cell lines and GES-1 cells detected by qRT-PCR. *, ** represents gastric cancer cell lines vs. GES-1, P  < .05, P < .01.
Figure 2.
Figure 2.
Interference of AQP-1 inhibited gastric cancer proliferation. (A) Transfection efficiency of siAQP1 #1 or #2 in AGS and MKN45 cells detected by qRT-PCR. ** represents siAQP1 #1 or #2 vs. siNC, P < .01. (B) Transfection efficiency of siAQP1 #1 or #2 in AGS and MKN45 cells detected by western blot. ** represents siAQP1 #1 or #2 vs. siNC, P < .01. (C) The effect of AQP-1 on cell proliferation of AGS and MKN45 cells detected by CCK8. *, ** represents siAQP1 vs. siNC, P < .05, P < .01. (D) The effect of AQP-1 on protein expression of PCNA and MCM2 in AGS and MKN45 cells detected by western blot. ** represents siAQP1 vs. siNC, P <  .01.
Figure 3.
Figure 3.
Interference of AQP-1 inhibited gastric cancer migration and invasion. (A) The effect of AQP-1 on cell migration of AGS and MKN45 cells detected by wound healing assay. ** represents siAQP1 vs. siNC, P < .01. (B) The effect of AQP-1 on cell invasion of AGS and MKN45 cells detected by transwell assay. ** represents siAQP1 vs. siNC, P <  .01.
Figure 4.
Figure 4.
Interference of AQP-1 inhibited GRB7-mediated RAS/ERK activation. (A) The effect of AQP-1 on protein expression of GRB7, p-GRB7, ERK and p-ERK in AGS and MKN45 cells detected by western blot. ** represents siAQP1 vs. siNC, P < .01. (B) The effect of AQP-1 on protein expression of active and total RAS in AGS and MKN45 cells detected by western blot. ** represents siAQP1 vs. siNC, P < .01.
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