Aquaporin 1 knockdown inhibits triple‑negative breast cancer cell proliferation and invasion in vitro and in vivo

Ji,Yinan; Liao,Xiaoming; Jiang,Yi; Wei,Wei; Yang,Huawei

doi:10.3892/ol.2021.12698

Aquaporin 1 knockdown inhibits triple‑negative breast cancer cell proliferation and invasion in vitro and in vivo

Authors:
- Yinan Ji
- Xiaoming Liao
- Yi Jiang
- Wei Wei
- Huawei Yang
View Affiliations

Affiliations: Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
Published online on: April 1, 2021 https://doi.org/10.3892/ol.2021.12698
Article Number: 437
Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Aquaporin 1 (AQP1) contributes to the progression of several cancer types, but its potential involvement in triple‑negative breast cancer (TNBC) is unclear. The aim of the present study was to examine the role of AQP1 in cell proliferation and invasion in TNBC. Reverse transcription‑quantitative PCR analysis and western blotting were used to detect AQP1 expression in different cell lines. A short hairpin (sh)RNA targeting AQP1 was established and transfected into MDA‑MB‑231 breast cancer cells. To investigate the effects of AQP1 knockdown, breast cancer cell proliferation, migration and invasion were evaluated by Cell Counting Kit‑8 and Transwell assays. Furthermore, the volume and weight of tumor xenografts in mice were measured to evaluate breast cancer growth ability. The results revealed that the levels of AQP1 were higher in the MDA‑MB‑231 cell line compared with those in other breast cancer cell lines (MCF‑7 and SK‑BR‑3) and a normal mammary epithelial cell line (MCF‑10A). The shRNA targeting AQP1 effectively downregulated AQP1 expression at the mRNA and protein levels, and markedly suppressed TNBC cell proliferation, migration and invasion in vitro, and tumor growth in vivo. These results suggested that AQP1 may serve as a potential therapeutic target in TNBC.

View Figures

View References

1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	DeSantis CE, Ma J, Goding Sauer A, Newman LA and Jemal A: Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 67:439–448. 2017. View Article : Google Scholar : PubMed/NCBI
3	Scott LC, Mobley LR, Kuo TM and Il'yasova D: Update on triple-negative breast cancer disparities for the United States: A population-based study from the United States cancer statistics database, 2010 through 2014. Cancer. 125:3412–3417. 2019. View Article : Google Scholar : PubMed/NCBI
4	Hwang KT, Kim J, Jung J, Chang JH, Chai YJ, Oh SW, Oh S, Kim YA, Park SB and Hwang KR: Impact of breast cancer subtypes on prognosis of women with operable invasive breast cancer: A population-based study using SEER database. Clin Cancer Res. 25:1970–1979. 2019.PubMed/NCBI
5	Verkman AS and Mitra AK: Structure and function of aquaporin water channels. Am J Physiol Renal Physiol. 278:F13–F28. 2000. View Article : Google Scholar : PubMed/NCBI
6	Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A and Nielsen S: Aquaporin water channels-from atomic structure to clinical medicine. J Physiol. 542:3–16. 2002. View Article : Google Scholar : PubMed/NCBI
7	Kang BW, Kim JG, Lee SJ, Chae YS and Jeong JY, Yoon GS, Park SY, Kim HJ, Park JS, Choi GS and Jeong JY: Expression of aquaporin-1, aquaporin-3, and aquaporin-5 correlates with nodal metastasis in colon cancer. Oncology. 88:369–376. 2015. View Article : Google Scholar : PubMed/NCBI
8	Thapa S, Chetry M, Huang K, Peng Y, Wang J, Wang J, Zhou Y, Shen Y, Xue Y and Ji K: Significance of aquaporins' expression in the prognosis of gastric cancer. Biosci Rep. 38:BSR201716872018. View Article : Google Scholar : PubMed/NCBI
9	Chetry M, Li S, Liu H, Hu X and Zhu X: Prognostic values of aquaporins mRNA expression in human ovarian cancer. Biosci Rep. 38:BSR201801082018. View Article : Google Scholar : PubMed/NCBI
10	Otterbach F, Callies R, Kimmig R, Schmid KW and Bánkfalvi A: Aquaporin 1 expression in invasive breast carcinomas. Pathologe. 29 (Suppl 2):S357–S362. 2008.(In German). View Article : Google Scholar
11	Otterbach F, Callies R, Adamzik M, Kimmig R, Siffert W, Schmid KW and Bankfalvi A: Aquaporin 1 (AQP1) expression is a novel characteristic feature of a particularly aggressive subgroup of basal-like breast carcinomas. Breast Cancer Res Treat. 120:67–76. 2010. View Article : Google Scholar : PubMed/NCBI
12	Qin F, Zhang H, Shao Y, Liu X, Yang L, Huang Y, Fu L, Gu F and Ma Y: Expression of aquaporin1, a water channel protein, in cytoplasm is negatively correlated with prognosis of breast cancer patients. Oncotarget. 7:8143–8154. 2016. View Article : Google Scholar : PubMed/NCBI
13	Zhu L, Ma N, Wang B, Wang L, Zhou C, Yan Y, He J and Ren Y: Significant prognostic values of aquaporin mRNA expression in breast cancer. Cancer Manag Res. 11:1503–1515. 2019. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Shi Z, Zhang T, Luo L, Zhao H, Cheng J, Xiang J and Zhao C: Aquaporins in human breast cancer: Identification and involvement in carcinogenesis of breast cancer. J Surg Oncol. 106:267–272. 2012. View Article : Google Scholar : PubMed/NCBI
16	Wang Y, Fan Y, Zheng C and Zhang X: Knockdown of AQP1 inhibits growth and invasion of human ovarian cancer cells. Mol Med Rep. 16:5499–5504. 2017. View Article : Google Scholar : PubMed/NCBI
17	Wei X and Dong J: Aquaporin 1 promotes the proliferation and migration of lung cancer cell in vitro. Oncol Rep. 34:1440–1448. 2015. View Article : Google Scholar : PubMed/NCBI
18	Guan Y, Chen J, Zhan Y and Lu H: Effects of dexamethasone on C6 cell proliferation, migration and invasion through the upregulation of AQP1. Oncol Lett. 15:7595–7602. 2018.PubMed/NCBI
19	Wu Z, Li S, Liu J, Shi Y, Wang J, Chen D, Luo L, Qian Y, Huang X and Wang H: RNAi-mediated silencing of AQP1 expression inhibited the proliferation, invasion and tumorigenesis of osteosarcoma cells. Cancer Biol Ther. 16:1332–1340. 2015. View Article : Google Scholar : PubMed/NCBI
20	Hu J and Verkman AS: Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. FASEB J. 20:1892–1894. 2006. View Article : Google Scholar : PubMed/NCBI
21	Hussain SA, Ganesan R, Reynolds G, Gross L, Stevens A, Pastorek J, Murray PG, Perunovic B, Anwar MS, Billingham L, et al: Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer. Br J Cancer. 96:104–109. 2007. View Article : Google Scholar : PubMed/NCBI
22	Verkman AS: Aquaporin water channels and endothelial cell function. J Anat. 200:617–627. 2002. View Article : Google Scholar : PubMed/NCBI
23	Verkman AS: Knock-out models reveal new aquaporin functions. Handb Exp Pharmacol. 359–381. 2009. View Article : Google Scholar : PubMed/NCBI
24	Verkman AS, Hara-Chikuma M and Papadopoulos MC: Aquaporins-new players in cancer biology. J Mol Med (Berl). 86:523–529. 2008. View Article : Google Scholar : PubMed/NCBI
25	Esteva-Font C, Jin BJ and Verkman AS: Aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in tumor-producing MMTV-PyVT mice. FASEB J. 28:1446–1453. 2014. View Article : Google Scholar : PubMed/NCBI
26	Nicchia GP, Stigliano C, Sparaneo A, Rossi A, Frigeri A and Svelto M: Inhibition of aquaporin-1 dependent angiogenesis impairs tumour growth in a mouse model of melanoma. J Mol Med (Berl). 91:613–623. 2013. View Article : Google Scholar : PubMed/NCBI
27	El Hindy N, Bankfalvi A, Herring A, Adamzik M, Lambertz N, Zhu Y, Siffert W, Sure U and Sandalcioglu IE: Correlation of aquaporin-1 water channel protein expression with tumor angiogenesis in human astrocytoma. Anticancer Res. 33:609–613. 2013.PubMed/NCBI