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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2013
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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) |
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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. |
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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 |
work_keys_str_mv |
AT yifanwang humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer AT xingyewu humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer AT qiangli humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer AT shangrongzhang humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer AT shujieli humanvoltagegatedprotonchannelhv1anewpotentialbiomarkerfordiagnosisandprognosisofcolorectalcancer |
_version_ |
1718375406102380544 |