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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Veröffentlicht in:PloS one 2013-08, Vol.8 (8), p.e70550-e70550
Hauptverfasser: Wang, Yifan, Wu, Xingye, Li, Qiang, Zhang, Shangrong, Li, Shu Jie
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Zhang, Shangrong
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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.
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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. 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prognosis</subject><subject>Medicine</subject><subject>Metabolites</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>NAD(P)H oxidase</subject><subject>Neutrophils</subject><subject>Oxidases</subject><subject>p53 Protein</subject><subject>Pathology</subject><subject>Patients</subject><subject>pH effects</subject><subject>Physics</subject><subject>Polyclonal antibodies</subject><subject>Polymerase chain reaction</subject><subject>Polyps</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Protons</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Solid tumors</subject><subject>Surgery</subject><subject>Tissues</subject><subject>Tumor cell lines</subject><subject>Tumor cells</subject><subject>Tumor 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Qiang</au><au>Zhang, Shangrong</au><au>Li, Shu Jie</au><au>Srivastava, Rakesh K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-08-05</date><risdate>2013</risdate><volume>8</volume><issue>8</issue><spage>e70550</spage><epage>e70550</epage><pages>e70550-e70550</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23940591</pmid><doi>10.1371/journal.pone.0070550</doi><tpages>e70550</tpages><oa>free_for_read</oa></addata></record>
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subjects Acidification
Acidosis
Adult
Aged
Antineoplastic drugs
Antitumor agents
Apoptosis
Bioindicators
Biology
Biomarkers
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biophysics
Biotechnology
Blotting, Western
Breast cancer
Cancer
Cancer metastasis
Cell Line
Cell migration
Cell Movement - genetics
Cell Movement - physiology
Chemotherapy
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - diagnosis
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Diagnosis
Drugs
Electric potential
Ethics
Extrusion
Female
Fluorescent Antibody Technique
Gastrointestinal diseases
Glycolysis
Health aspects
Humans
Hydrogen-Ion Concentration
Hypoxia
Immunocytochemistry
Immunohistochemistry
Ion Channels - genetics
Ion Channels - metabolism
Lymph nodes
Male
Medical diagnosis
Medical prognosis
Medicine
Metabolites
Metastases
Metastasis
Middle Aged
NAD(P)H oxidase
Neutrophils
Oxidases
p53 Protein
Pathology
Patients
pH effects
Physics
Polyclonal antibodies
Polymerase chain reaction
Polyps
Prognosis
Proteins
Protons
Real-Time Polymerase Chain Reaction
Ribonucleic acid
RNA
Rodents
siRNA
Solid tumors
Surgery
Tissues
Tumor cell lines
Tumor cells
Tumor proteins
Tumors
Voltage
title Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer
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