Critical role of aquaporin-3 in epidermal growth factor-induced migration of colorectal carcinoma cells and its clinical significance

Li,Ang; Lu,Dehong; Zhang,Yupeng; Li,Jia; Fang,Yu; Li,Fei; Sun,Jiabang

doi:10.3892/or.2012.2144

Critical role of aquaporin-3 in epidermal growth factor-induced migration of colorectal carcinoma cells and its clinical significance

Authors:
- Ang Li
- Dehong Lu
- Yupeng Zhang
- Jia Li
- Yu Fang
- Fei Li
- Jiabang Sun
View Affiliations

Affiliations: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China, Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China
Published online on: November 15, 2012 https://doi.org/10.3892/or.2012.2144
Pages: 535-540

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

Aquaporins (AQPs) are a family of small, integral membrane proteins that have been shown to play an important role in tumor development and metastasis. Several studies have demonstrated that expression of AQP3 contributes to the enhanced migration of epithelial cells and is related to differentiation, metastasis and vascular invasion in lung and gastric cancer. Therefore, we investigated whether AQP3 could enhance human colorectal carcinoma cell migration and we examined the role of AQP3 in the prognosis of colorectal carcinoma. Our results showed that human epidermal growth factor (hEGF) increased the expression of AQP3 and, subsequently, the migration ability of human colorectal carcinoma cells HCT116 in a dose- and time-dependent manner. The enhanced migration ability of HCT116 cells was blocked by the AQP3 inhibitor, CuSO4. Overexpression of AQP3 induced by hEGF was inhibited by a PI3K/AKT inhibitor, LY294002, but the ERK inhibitor U0126 had a minor effect on the hEGF-induced AQP3 upregulation. Immunohistochemical staining of the cancer tissues and corresponding normal tissues showed that AQP3 expression in cancer tissue was higher compared to that in normal tissue. The expression intensity of AQP3 was associated with the differentiation, lymph node and distant metastasis of colorectal carcinoma patients. Our results suggest that AQP3 overexpression could facilitate colorectal carcinoma cell migration and AQP3 may be considered a potential indicator and therapeutic target for colon tumor metastasis and prognosis.

View Figures

View References

1	Remontet L, Esteve J, Bouvier AM, et al: Cancer incidence and mortality in France over the period 1978–2000. Rev Epidemiol Sante Publique. 51:3–30. 2003.
2	Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar
3	Giuliani F, De Vita F, Colucci G and Pisconti S: Maintenance therapy in colon cancer. Cancer Treat Rev. 36(Suppl 3): S42–S45. 2010. View Article : Google Scholar
4	Agre P: The aquaporin water channels. Proc Am Thorac Soc. 3:5–13. 2006. View Article : Google Scholar
5	Magni F, Sarto C, Ticozzi D, et al: Proteomic knowledge of human aquaporins. Proteomics. 6:5637–5649. 2006. View Article : Google Scholar : PubMed/NCBI
6	Hara-Chikuma M and Verkman AS: Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing. J Mol Med. 86:221–231. 2008. View Article : Google Scholar : PubMed/NCBI
7	Nakahigashi K, Kabashima K, Ikoma A, Verkman AS, Miyachi Y and Hara-Chikuma M: Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia. J Invest Dermatol. 131:865–873. 2011. View Article : Google Scholar : PubMed/NCBI
8	Huang Y, Zhu Z, Sun M, et al: Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells. Cancer Biol Ther. 9:1000–1007. 2010. View Article : Google Scholar : PubMed/NCBI
9	Kusayama M, Wada K, Nagata M, et al: Critical role of aquaporin 3 on growth of human esophageal and oral squamous cell carcinoma. Cancer Sci. 102:1128–1136. 2011. View Article : Google Scholar : PubMed/NCBI
10	Bogenrieder T and Herlyn M: Axis of evil: molecular mechanisms of cancer metastasis. Oncogene. 22:6524–6536. 2003. View Article : Google Scholar : PubMed/NCBI
11	Fischer H, Stenling R, Rubio C and Lindblom A: Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiol. 1:12001. View Article : Google Scholar : PubMed/NCBI
12	Ishibashi K, Sasaki S, Saito F, Ikeuchi T and Marumo F: Structure and chromosomal localization of a human water channel (AQP3) gene. Genomics. 27:352–354. 1995. View Article : Google Scholar : PubMed/NCBI
13	Hasegawa H, Lian SC, Finkbeiner WE and Verkman AS: Extrarenal tissue distribution of CHIP28 water channels by in situ hybridization and antibody staining. Am J Physiol. 266:C893–C903. 1994.PubMed/NCBI
14	Moon C, Soria JC, Jang SJ, et al: Involvement of aquaporins in colorectal carcinogenesis. Oncogene. 22:6699–6703. 2003. View Article : Google Scholar : PubMed/NCBI
15	Kim M, Yoon S, Lee S, et al: Gremlin-1 induces BMP-independent tumor cell proliferation, migration, and invasion. PLoS One. 7:e351002012. View Article : Google Scholar : PubMed/NCBI
16	Du J, Cheng B, Zhu X and Ling C: Ginsenoside Rg1, a novel glucocorticoid receptor agonist of plant origin, maintains glucocorticoid efficacy with reduced side effects. J Immunol. 187:942–950. 2011. View Article : Google Scholar : PubMed/NCBI
17	Fromowitz FB, Viola MV, Chao S, et al: ras p21 expression in the progression of breast cancer. Hum Pathol. 18:1268–1275. 1987. View Article : Google Scholar : PubMed/NCBI
18	Cohen S and Elliott GA: The stimulation of epidermal keratinization by a protein isolated from the submaxillary gland of the mouse. J Invest Dermatol. 40:1–5. 1963.PubMed/NCBI
19	Pryczynicz A, Guzinska-Ustymowicz K, Kemona A and Czyzewska J: Expression of EGF and EGFR strongly correlates with metastasis of pancreatic ductal carcinoma. Anticancer Res. 28:1399–1404. 2008.PubMed/NCBI
20	Jin Y, Li JP, Tang LY, et al: Protein expression and significance of VEGF, EGFR and MMP-9 in non-small cell lung carcinomas. Asian Pac J Cancer Prev. 12:1473–1476. 2011.PubMed/NCBI
21	Ji C, Cao C, Lu S, et al: Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells. Cancer Chemother Pharmacol. 62:857–865. 2008. View Article : Google Scholar : PubMed/NCBI
22	Ciardiello F and Tortora G: A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res. 7:2958–2970. 2001.PubMed/NCBI
23	Wang J, Gui Z, Deng L, et al: c-Met upregulates aquaporin 3 expression in human gastric carcinoma cells via the ERK signalling pathway. Cancer Lett. 319:109–117. 2012. View Article : Google Scholar : PubMed/NCBI
24	Liu YL, Matsuzaki T, Nakazawa T, et al: Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. Hum Pathol. 38:171–178. 2007. View Article : Google Scholar : PubMed/NCBI
25	Shen L, Zhu Z, Huang Y, et al: Expression profile of multiple aquaporins in human gastric carcinoma and its clinical significance. Biomed Pharmacother. 64:313–318. 2010. View Article : Google Scholar : PubMed/NCBI