CD44v6 engages in colorectal cancer progression
CD44 is a transmembrane glycoprotein. When the CD44 gene is expressed, its pre-messenger RNA (mRNA) can be alternatively spliced into mature mRNAs that encode several CD44 isoforms. The mRNA assembles with ten standard exons, and the sixth variant exon encodes CD44v6, which engages in a variety of b...
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| description | CD44 is a transmembrane glycoprotein. When the
CD44
gene is expressed, its pre-messenger RNA (mRNA) can be alternatively spliced into mature mRNAs that encode several CD44 isoforms. The mRNA assembles with ten standard exons, and the sixth variant exon encodes CD44v6, which engages in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. Mechanistically, CD44v6 interacts with hyaluronic acid (HA) or osteopontin, or it acts as a coreceptor for various cytokines, such as epidermal growth factor, vascular endothelial growth factor, hepatocyte growth factor, and C-X-C motif chemokine 12. In this context, the receptor tyrosine kinase or G protein-coupled receptor-associated signaling pathways, including mitogen-activated protein kinase/extracellular-signal-regulated kinase and phosphoinositide-3-kinase/Akt, are activated. Using these actions, homeostasis or regeneration can be facilitated among normal tissues. However, overexpression of the mature mRNA encoding CD44v6 can induce cancer progression. For example, CD44v6 assists colorectal cancer stem cells in colonization, invasion, and metastasis. Overexpression of CD44v6 predicts poor prognosis in patients with colorectal cancer, as patients with a large number of CD44v6-positive cells in their tumors are generally diagnosed at late stages. Thus, the clinical significance of CD44v6 in colorectal cancer deserves consideration. Preclinical results have indicated satisfactory efficacies of anti-CD44 therapy among several cancers, including prostate cancer, pancreatic cancer, and gastric cancer. Moreover, clinical trials aiming to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and toxicity of a commercialized anti-CD44 monoclonal antibody developed by Roche (RO5429083) have been conducted among patients with CD44-expressing malignant tumors, and a clinical trial focusing on the dose escalation of this antibody is ongoing. Thus, we are hopeful that anti-CD44 therapy will be applied in the treatment of colorectal cancer in the future. |
| doi_str_mv | 10.1038/s41419-018-1265-7 |
| format | Article |
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CD44
gene is expressed, its pre-messenger RNA (mRNA) can be alternatively spliced into mature mRNAs that encode several CD44 isoforms. The mRNA assembles with ten standard exons, and the sixth variant exon encodes CD44v6, which engages in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. Mechanistically, CD44v6 interacts with hyaluronic acid (HA) or osteopontin, or it acts as a coreceptor for various cytokines, such as epidermal growth factor, vascular endothelial growth factor, hepatocyte growth factor, and C-X-C motif chemokine 12. In this context, the receptor tyrosine kinase or G protein-coupled receptor-associated signaling pathways, including mitogen-activated protein kinase/extracellular-signal-regulated kinase and phosphoinositide-3-kinase/Akt, are activated. Using these actions, homeostasis or regeneration can be facilitated among normal tissues. However, overexpression of the mature mRNA encoding CD44v6 can induce cancer progression. For example, CD44v6 assists colorectal cancer stem cells in colonization, invasion, and metastasis. Overexpression of CD44v6 predicts poor prognosis in patients with colorectal cancer, as patients with a large number of CD44v6-positive cells in their tumors are generally diagnosed at late stages. Thus, the clinical significance of CD44v6 in colorectal cancer deserves consideration. Preclinical results have indicated satisfactory efficacies of anti-CD44 therapy among several cancers, including prostate cancer, pancreatic cancer, and gastric cancer. Moreover, clinical trials aiming to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and toxicity of a commercialized anti-CD44 monoclonal antibody developed by Roche (RO5429083) have been conducted among patients with CD44-expressing malignant tumors, and a clinical trial focusing on the dose escalation of this antibody is ongoing. Thus, we are hopeful that anti-CD44 therapy will be applied in the treatment of colorectal cancer in the future.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-018-1265-7</identifier><identifier>PMID: 30631039</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1504/1885 ; 631/67/322 ; 692/53/2422 ; AKT protein ; Alternative splicing ; Angiogenesis ; Antibodies ; Antibodies, Monoclonal, Humanized - therapeutic use ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; CD44 antigen ; Cell Biology ; Cell Culture ; Cell migration ; Chemokines ; Clinical trials ; Colonization ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - mortality ; Cytokines ; Disease Progression ; Drug Resistance, Neoplasm - genetics ; Epidermal growth factor ; Exons ; Exons - drug effects ; Exons - genetics ; Gastric cancer ; Gene Expression ; Growth factors ; Hepatocyte growth factor ; Homeostasis ; Humans ; Hyaluronan Receptors - genetics ; Hyaluronan Receptors - immunology ; Hyaluronan Receptors - metabolism ; Hyaluronic acid ; Hyaluronic Acid - metabolism ; Immunology ; Isoforms ; Kinases ; Life Sciences ; Metastases ; Monoclonal antibodies ; mRNA ; Osteopontin - metabolism ; Pancreatic cancer ; Patients ; Pharmacokinetics ; Prognosis ; Prostate cancer ; Protein Isoforms - metabolism ; Review ; Review Article ; Stem cells ; Survival Rate ; Toxicity ; Tumors ; Vascular endothelial growth factor</subject><ispartof>Cell death & disease, 2019-01, Vol.10 (1), p.30, Article 30</ispartof><rights>The Author(s) 2018</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-a987f3f89d5b408f9009488b0ca718d220ea2a78f940e98a365debf4103037b53</citedby><cites>FETCH-LOGICAL-c584t-a987f3f89d5b408f9009488b0ca718d220ea2a78f940e98a365debf4103037b53</cites><orcidid>0000-0001-9047-7942</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328617/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328617/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30631039$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Lixin</creatorcontrib><creatorcontrib>Dong, Lihua</creatorcontrib><creatorcontrib>Chang, Pengyu</creatorcontrib><title>CD44v6 engages in colorectal cancer progression</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>CD44 is a transmembrane glycoprotein. When the
CD44
gene is expressed, its pre-messenger RNA (mRNA) can be alternatively spliced into mature mRNAs that encode several CD44 isoforms. The mRNA assembles with ten standard exons, and the sixth variant exon encodes CD44v6, which engages in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. Mechanistically, CD44v6 interacts with hyaluronic acid (HA) or osteopontin, or it acts as a coreceptor for various cytokines, such as epidermal growth factor, vascular endothelial growth factor, hepatocyte growth factor, and C-X-C motif chemokine 12. In this context, the receptor tyrosine kinase or G protein-coupled receptor-associated signaling pathways, including mitogen-activated protein kinase/extracellular-signal-regulated kinase and phosphoinositide-3-kinase/Akt, are activated. Using these actions, homeostasis or regeneration can be facilitated among normal tissues. However, overexpression of the mature mRNA encoding CD44v6 can induce cancer progression. For example, CD44v6 assists colorectal cancer stem cells in colonization, invasion, and metastasis. Overexpression of CD44v6 predicts poor prognosis in patients with colorectal cancer, as patients with a large number of CD44v6-positive cells in their tumors are generally diagnosed at late stages. Thus, the clinical significance of CD44v6 in colorectal cancer deserves consideration. Preclinical results have indicated satisfactory efficacies of anti-CD44 therapy among several cancers, including prostate cancer, pancreatic cancer, and gastric cancer. Moreover, clinical trials aiming to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and toxicity of a commercialized anti-CD44 monoclonal antibody developed by Roche (RO5429083) have been conducted among patients with CD44-expressing malignant tumors, and a clinical trial focusing on the dose escalation of this antibody is ongoing. Thus, we are hopeful that anti-CD44 therapy will be applied in the treatment of colorectal cancer in the future.</description><subject>631/67/1504/1885</subject><subject>631/67/322</subject><subject>692/53/2422</subject><subject>AKT protein</subject><subject>Alternative splicing</subject><subject>Angiogenesis</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>CD44 antigen</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell migration</subject><subject>Chemokines</subject><subject>Clinical trials</subject><subject>Colonization</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Cytokines</subject><subject>Disease Progression</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Epidermal growth factor</subject><subject>Exons</subject><subject>Exons - drug effects</subject><subject>Exons - genetics</subject><subject>Gastric cancer</subject><subject>Gene Expression</subject><subject>Growth factors</subject><subject>Hepatocyte growth factor</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Hyaluronan Receptors - genetics</subject><subject>Hyaluronan Receptors - immunology</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Hyaluronic acid</subject><subject>Hyaluronic Acid - metabolism</subject><subject>Immunology</subject><subject>Isoforms</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Metastases</subject><subject>Monoclonal antibodies</subject><subject>mRNA</subject><subject>Osteopontin - metabolism</subject><subject>Pancreatic cancer</subject><subject>Patients</subject><subject>Pharmacokinetics</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Protein Isoforms - metabolism</subject><subject>Review</subject><subject>Review Article</subject><subject>Stem cells</subject><subject>Survival Rate</subject><subject>Toxicity</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kM1LwzAAxYMobsz9AV6k4LkuX02TiyDzEwZe9BzSNK0dXVKTbuB_b0rnnAdzSeC9_N7jAXCJ4A2ChC8CRRSJFCKeIsyyND8BUwwpSinn4vToPQHzENYwHkIgztg5mBDISISIKVgs7yndscTYWtUmJI1NtGudN7pXbaKV1cYnnXe1NyE0zl6As0q1wcz39wy8Pz68LZ_T1evTy_JuleqM0z5VgucVqbgos4JCXgkIRexSQK1yxEuMoVFY5VGg0AiuCMtKU1Q0loIkLzIyA7cjt9sWG1NqY3uvWtn5ZqP8l3SqkX8V23zI2u0kI5gzlEfA9R7g3efWhF6u3dbb2FlixBjCcbMhBo0u7V0I3lSHBATlMLMcZ5ZxZjnMLAfy1XG1w4-fUaMBj4YQJVsb_xv9P_UbWRKGbA</recordid><startdate>20190110</startdate><enddate>20190110</enddate><creator>Ma, Lixin</creator><creator>Dong, Lihua</creator><creator>Chang, Pengyu</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9047-7942</orcidid></search><sort><creationdate>20190110</creationdate><title>CD44v6 engages in colorectal cancer progression</title><author>Ma, Lixin ; Dong, Lihua ; Chang, Pengyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-a987f3f89d5b408f9009488b0ca718d220ea2a78f940e98a365debf4103037b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>631/67/1504/1885</topic><topic>631/67/322</topic><topic>692/53/2422</topic><topic>AKT protein</topic><topic>Alternative splicing</topic><topic>Angiogenesis</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>CD44 antigen</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell migration</topic><topic>Chemokines</topic><topic>Clinical trials</topic><topic>Colonization</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Cytokines</topic><topic>Disease Progression</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Epidermal growth factor</topic><topic>Exons</topic><topic>Exons - drug effects</topic><topic>Exons - genetics</topic><topic>Gastric cancer</topic><topic>Gene Expression</topic><topic>Growth factors</topic><topic>Hepatocyte growth factor</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Hyaluronan Receptors - genetics</topic><topic>Hyaluronan Receptors - immunology</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Hyaluronic acid</topic><topic>Hyaluronic Acid - metabolism</topic><topic>Immunology</topic><topic>Isoforms</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Metastases</topic><topic>Monoclonal antibodies</topic><topic>mRNA</topic><topic>Osteopontin - metabolism</topic><topic>Pancreatic cancer</topic><topic>Patients</topic><topic>Pharmacokinetics</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Protein Isoforms - metabolism</topic><topic>Review</topic><topic>Review Article</topic><topic>Stem cells</topic><topic>Survival Rate</topic><topic>Toxicity</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Lixin</creatorcontrib><creatorcontrib>Dong, Lihua</creatorcontrib><creatorcontrib>Chang, Pengyu</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Lixin</au><au>Dong, Lihua</au><au>Chang, Pengyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD44v6 engages in colorectal cancer progression</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-01-10</date><risdate>2019</risdate><volume>10</volume><issue>1</issue><spage>30</spage><pages>30-</pages><artnum>30</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>CD44 is a transmembrane glycoprotein. When the
CD44
gene is expressed, its pre-messenger RNA (mRNA) can be alternatively spliced into mature mRNAs that encode several CD44 isoforms. The mRNA assembles with ten standard exons, and the sixth variant exon encodes CD44v6, which engages in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. Mechanistically, CD44v6 interacts with hyaluronic acid (HA) or osteopontin, or it acts as a coreceptor for various cytokines, such as epidermal growth factor, vascular endothelial growth factor, hepatocyte growth factor, and C-X-C motif chemokine 12. In this context, the receptor tyrosine kinase or G protein-coupled receptor-associated signaling pathways, including mitogen-activated protein kinase/extracellular-signal-regulated kinase and phosphoinositide-3-kinase/Akt, are activated. Using these actions, homeostasis or regeneration can be facilitated among normal tissues. However, overexpression of the mature mRNA encoding CD44v6 can induce cancer progression. For example, CD44v6 assists colorectal cancer stem cells in colonization, invasion, and metastasis. Overexpression of CD44v6 predicts poor prognosis in patients with colorectal cancer, as patients with a large number of CD44v6-positive cells in their tumors are generally diagnosed at late stages. Thus, the clinical significance of CD44v6 in colorectal cancer deserves consideration. Preclinical results have indicated satisfactory efficacies of anti-CD44 therapy among several cancers, including prostate cancer, pancreatic cancer, and gastric cancer. Moreover, clinical trials aiming to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and toxicity of a commercialized anti-CD44 monoclonal antibody developed by Roche (RO5429083) have been conducted among patients with CD44-expressing malignant tumors, and a clinical trial focusing on the dose escalation of this antibody is ongoing. Thus, we are hopeful that anti-CD44 therapy will be applied in the treatment of colorectal cancer in the future.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30631039</pmid><doi>10.1038/s41419-018-1265-7</doi><orcidid>https://orcid.org/0000-0001-9047-7942</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/1504/1885 631/67/322 692/53/2422 AKT protein Alternative splicing Angiogenesis Antibodies Antibodies, Monoclonal, Humanized - therapeutic use Apoptosis Biochemistry Biomedical and Life Sciences CD44 antigen Cell Biology Cell Culture Cell migration Chemokines Clinical trials Colonization Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - mortality Cytokines Disease Progression Drug Resistance, Neoplasm - genetics Epidermal growth factor Exons Exons - drug effects Exons - genetics Gastric cancer Gene Expression Growth factors Hepatocyte growth factor Homeostasis Humans Hyaluronan Receptors - genetics Hyaluronan Receptors - immunology Hyaluronan Receptors - metabolism Hyaluronic acid Hyaluronic Acid - metabolism Immunology Isoforms Kinases Life Sciences Metastases Monoclonal antibodies mRNA Osteopontin - metabolism Pancreatic cancer Patients Pharmacokinetics Prognosis Prostate cancer Protein Isoforms - metabolism Review Review Article Stem cells Survival Rate Toxicity Tumors Vascular endothelial growth factor |
| title | CD44v6 engages in colorectal cancer progression |
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