Role of human aquaporin 5 in colorectal carcinogenesis

Koo Kang Sung, Kwang Chae Young, Janghee Woo, Sook Kim Myoung, Chul Park Jong, Juna Lee, Jean Charles Soria, Jin Jang Se, David Sidransky, Chulso Moon

Research output: Contribution to journalArticle

Abstract

While overexpression of several aquaporins (AQPs) has been reported in different types of human cancer, the role of AQPs in carcinogenesis has not been clearly defined. Here, by immunochemistry, we have found expression of AQP5 protein in 62.8% (59/94) of resected colon cancer tissue samples as well as association of AQP5 with liver metastasis. We then demonstrated that overexpression of human AQP5 (hAQP5) induces cell proliferation in colon cancer cells. Overexpression of wild-type hAQP5 increased proliferation and phosphorylation of extracellular signal-regulated kinase-1/2 in HCT116 colon cancer cells whereas these phenomena in hAQP5 mutants (N185D and S156A) were diminished, indicating that both membrane association and serine/threonine phosphorylation of AQP5 are required for proper function. Interestingly, overexpression of AQP1 and AQP3 showed no differences in extracellular signal-regulated kinase-1/2 phosphorylation, suggesting that AQP5, unlike AQP1, may be involved in signal transduction. Moreover, hAQP5-overexpressing cells showed an increase in retinoblastoma protein phosphorylation through the formation of a nuclear complex with cyclin D1 and CDK4. Small interfering RNA analysis confirmed that hAQP5 activates the Ras signaling pathway. These data not only describe the induction of hAQP5 expression during colorectal carcinogenesis but also provide a molecular mechanism for colon cancer development through the interaction of hAQP5 with the Ras/extracellular signal-regulated kinase/retinoblastoma protein signaling pathway, identifying hAQP5 as a novel therapeutic target.

Original languageEnglish (US)
Pages (from-to)518-525
Number of pages8
JournalAmerican Journal of Pathology
Volume173
Issue number2
DOIs
StatePublished - Aug 2008

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Aquaporin 5
Carcinogenesis
Colonic Neoplasms
Phosphorylation
Retinoblastoma Protein
Aquaporins
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Immunochemistry
Cyclin D1
Extracellular Signal-Regulated MAP Kinases
Threonine
Serine
Small Interfering RNA
Signal Transduction
Cell Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Sung, K. K., Young, K. C., Woo, J., Myoung, S. K., Jong, C. P., Lee, J., ... Moon, C. (2008). Role of human aquaporin 5 in colorectal carcinogenesis. American Journal of Pathology, 173(2), 518-525. https://doi.org/10.2353/ajpath.2008.071198

Role of human aquaporin 5 in colorectal carcinogenesis. / Sung, Koo Kang; Young, Kwang Chae; Woo, Janghee; Myoung, Sook Kim; Jong, Chul Park; Lee, Juna; Soria, Jean Charles; Se, Jin Jang; Sidransky, David; Moon, Chulso.

In: American Journal of Pathology, Vol. 173, No. 2, 08.2008, p. 518-525.

Research output: Contribution to journalArticle

Sung, KK, Young, KC, Woo, J, Myoung, SK, Jong, CP, Lee, J, Soria, JC, Se, JJ, Sidransky, D & Moon, C 2008, 'Role of human aquaporin 5 in colorectal carcinogenesis', American Journal of Pathology, vol. 173, no. 2, pp. 518-525. https://doi.org/10.2353/ajpath.2008.071198
Sung KK, Young KC, Woo J, Myoung SK, Jong CP, Lee J et al. Role of human aquaporin 5 in colorectal carcinogenesis. American Journal of Pathology. 2008 Aug;173(2):518-525. https://doi.org/10.2353/ajpath.2008.071198
Sung, Koo Kang ; Young, Kwang Chae ; Woo, Janghee ; Myoung, Sook Kim ; Jong, Chul Park ; Lee, Juna ; Soria, Jean Charles ; Se, Jin Jang ; Sidransky, David ; Moon, Chulso. / Role of human aquaporin 5 in colorectal carcinogenesis. In: American Journal of Pathology. 2008 ; Vol. 173, No. 2. pp. 518-525.
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