Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells

Hypoxia induces epithelial‐mesenchymal transition (EMT) in tumorigenesis. A‐kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EM...

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Veröffentlicht in:Journal of cellular biochemistry 2018-12, Vol.119 (12), p.10013-10020
Hauptverfasser: Li, Quanying, Tang, Hongna, Hu, Fangfang, Qin, Changjiang
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creator Li, Quanying
Tang, Hongna
Hu, Fangfang
Qin, Changjiang
description Hypoxia induces epithelial‐mesenchymal transition (EMT) in tumorigenesis. A‐kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia‐inducible factor‐1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia‐induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/β‐catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia‐induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer. Knockdown of A‐kinase anchor protein 4 AKAP4 inhibits hypoxia‐induced epithelial‐mesenchymal transition in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer.
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A‐kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia‐inducible factor‐1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia‐induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/β‐catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia‐induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer. Knockdown of A‐kinase anchor protein 4 AKAP4 inhibits hypoxia‐induced epithelial‐mesenchymal transition in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.27331</identifier><identifier>PMID: 30145836</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>A Kinase Anchor Proteins - metabolism ; A‐kinase anchor protein 4 (AKAP4) ; Cancer ; Catenin ; Cell Line, Tumor ; Cell Movement ; Deactivation ; Epithelial-Mesenchymal Transition ; epithelial‐to‐mesenchymal transition (EMT) ; Gastric cancer ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia ; Inactivation ; Kinases ; Mesenchyme ; Proteins ; Signal transduction ; Stomach Neoplasms - genetics ; Stomach Neoplasms - metabolism ; Therapeutic applications ; Tumor cell lines ; Tumorigenesis ; Wnt protein ; Wnt Signaling Pathway</subject><ispartof>Journal of cellular biochemistry, 2018-12, Vol.119 (12), p.10013-10020</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3531-1ac370b5ea4119e70d756f6de3e6abfb45032e1e0d11ca7707a3b6e985ec40143</citedby><cites>FETCH-LOGICAL-c3531-1ac370b5ea4119e70d756f6de3e6abfb45032e1e0d11ca7707a3b6e985ec40143</cites><orcidid>0000-0003-0363-2233</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.27331$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.27331$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30145836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Quanying</creatorcontrib><creatorcontrib>Tang, Hongna</creatorcontrib><creatorcontrib>Hu, Fangfang</creatorcontrib><creatorcontrib>Qin, Changjiang</creatorcontrib><title>Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells</title><title>Journal of cellular biochemistry</title><addtitle>J Cell Biochem</addtitle><description>Hypoxia induces epithelial‐mesenchymal transition (EMT) in tumorigenesis. A‐kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia‐inducible factor‐1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia‐induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/β‐catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia‐induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer. Knockdown of A‐kinase anchor protein 4 AKAP4 inhibits hypoxia‐induced epithelial‐mesenchymal transition in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. 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Tang, Hongna ; Hu, Fangfang ; Qin, Changjiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3531-1ac370b5ea4119e70d756f6de3e6abfb45032e1e0d11ca7707a3b6e985ec40143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>A Kinase Anchor Proteins - metabolism</topic><topic>A‐kinase anchor protein 4 (AKAP4)</topic><topic>Cancer</topic><topic>Catenin</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Deactivation</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>epithelial‐to‐mesenchymal transition (EMT)</topic><topic>Gastric cancer</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Inactivation</topic><topic>Kinases</topic><topic>Mesenchyme</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Therapeutic applications</topic><topic>Tumor cell lines</topic><topic>Tumorigenesis</topic><topic>Wnt protein</topic><topic>Wnt Signaling Pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Quanying</creatorcontrib><creatorcontrib>Tang, Hongna</creatorcontrib><creatorcontrib>Hu, Fangfang</creatorcontrib><creatorcontrib>Qin, Changjiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; 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A‐kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia‐inducible factor‐1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia‐induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/β‐catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia‐induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer. Knockdown of A‐kinase anchor protein 4 AKAP4 inhibits hypoxia‐induced epithelial‐mesenchymal transition in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30145836</pmid><doi>10.1002/jcb.27331</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0363-2233</orcidid></addata></record>
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subjects A Kinase Anchor Proteins - metabolism
A‐kinase anchor protein 4 (AKAP4)
Cancer
Catenin
Cell Line, Tumor
Cell Movement
Deactivation
Epithelial-Mesenchymal Transition
epithelial‐to‐mesenchymal transition (EMT)
Gastric cancer
Gene Expression Regulation, Neoplastic
Humans
Hypoxia
Inactivation
Kinases
Mesenchyme
Proteins
Signal transduction
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Therapeutic applications
Tumor cell lines
Tumorigenesis
Wnt protein
Wnt Signaling Pathway
title Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells
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