Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.

Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s). The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons w...

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Autores principales: Yifan Wang, Xingye Wu, Qiang Li, Shangrong Zhang, Shu Jie Li
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/158edd4622584721b802255c4052c07b
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spelling oai:doaj.org-article:158edd4622584721b802255c4052c07b2021-12-02T20:05:49ZHuman voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.1932-620310.1371/journal.pone.0070550https://doaj.org/article/158edd4622584721b802255c4052c07b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23940591/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s). The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons with protons. Here, we showed for the first time, that Hv1 expression is increased in colorectal tumor tissues and cell lines, associated with poor prognosis. Immunohistochemistry showed that Hv1 is strongly expressed in adenocarcinomas but not or lowly expressed in normal colorectal or hyperplastic polyps. Hv1 expression in colorectal cancer is significantly associated with the tumor size, tumor classification, lymph node status, clinical stage and p53 status. High Hv1 expression is associated significantly with shorter overall and recurrence-free survival. Furthermore, real-time RT-PCR and immunocytochemistry showed that Hv1 is highly expressed in colorectal cancer cell lines, SW620, HT29, LS174T and Colo205, but not in SW480. Inhibitions of Hv1 expression and activity in the highly metastatic SW620 cells by small interfering RNA (siRNA) and Zn(2+) respectively, markedly decrease the cell invasion and migration, restraint proton extrusion and the intracellular pH recovery. Our results suggest that Hv1 may be used as a potential biomarker for diagnosis and prognosis of colorectal carcinoma, and a potential target for anticancer drugs in colorectal cancer therapy.Yifan WangXingye WuQiang LiShangrong ZhangShu Jie LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70550 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yifan Wang
Xingye Wu
Qiang Li
Shangrong Zhang
Shu Jie Li
Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.
description Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s). The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons with protons. Here, we showed for the first time, that Hv1 expression is increased in colorectal tumor tissues and cell lines, associated with poor prognosis. Immunohistochemistry showed that Hv1 is strongly expressed in adenocarcinomas but not or lowly expressed in normal colorectal or hyperplastic polyps. Hv1 expression in colorectal cancer is significantly associated with the tumor size, tumor classification, lymph node status, clinical stage and p53 status. High Hv1 expression is associated significantly with shorter overall and recurrence-free survival. Furthermore, real-time RT-PCR and immunocytochemistry showed that Hv1 is highly expressed in colorectal cancer cell lines, SW620, HT29, LS174T and Colo205, but not in SW480. Inhibitions of Hv1 expression and activity in the highly metastatic SW620 cells by small interfering RNA (siRNA) and Zn(2+) respectively, markedly decrease the cell invasion and migration, restraint proton extrusion and the intracellular pH recovery. Our results suggest that Hv1 may be used as a potential biomarker for diagnosis and prognosis of colorectal carcinoma, and a potential target for anticancer drugs in colorectal cancer therapy.
format article
author Yifan Wang
Xingye Wu
Qiang Li
Shangrong Zhang
Shu Jie Li
author_facet Yifan Wang
Xingye Wu
Qiang Li
Shangrong Zhang
Shu Jie Li
author_sort Yifan Wang
title Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.
title_short Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.
title_full Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.
title_fullStr Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.
title_full_unstemmed Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.
title_sort human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/158edd4622584721b802255c4052c07b
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AT xingyewu humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer
AT qiangli humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer
AT shangrongzhang humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer
AT shujieli humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer
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