Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression
Cortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to stu...
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| Veröffentlicht in: | Modern pathology 2010-02, Vol.23 (2), p.187-196 |
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| description | Cortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to study the role of cortactin in melanocytic tumor progression using immunohistochemistry on human tissues. The results reveal quantitative differences between benign and malignant lesions. Significantly higher cortactin expression is found in melanomas than in nevi (
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| doi_str_mv | 10.1038/modpathol.2009.157 |
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P
<0.0001), with levels greater in metastatic than in invasive melanomas (
P
<0.05). Qualitatively, tumor tissues often show aberrant cortactin localization at the cell periphery, corresponding to its colocalization with filamentous actin in cell cortex of cultured melanoma cells. This suggests an additional level of protein dysregulation. Furthermore, in patients with metastatic disease, high-level cortactin expression correlates with poor disease-specific survival. Our data, in conjunction with outcome data on several other types of human cancers and experimental data from melanoma cell lines, supports a potential role of aberrant cortactin expression in melanoma tumor progression and a rational for targeting key elements of actin-signaling pathway for developmental therapeutics in melanomas.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2009.157</identifier><identifier>PMID: 19898426</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adapter proteins ; Automation ; Biomarkers, Tumor - analysis ; Cancer ; Cell cycle ; Cortactin - biosynthesis ; Cytoskeleton ; Cytoskeleton - genetics ; Cytoskeleton - pathology ; Disease Progression ; Fluorescent Antibody Technique ; Gene amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kaplan-Meier Estimate ; Kinases ; Laboratory Medicine ; Medicine & Public Health ; Melanoma ; Melanoma - genetics ; Melanoma - metabolism ; Melanoma - pathology ; Metastasis ; Neurosciences ; Nevus - metabolism ; Nevus - pathology ; Oncology ; original-article ; Pathology ; Precancerous Conditions - metabolism ; Precancerous Conditions - pathology ; Prognosis ; Skin Neoplasms - genetics ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Tissue Array Analysis ; Tumorigenesis ; Tumors</subject><ispartof>Modern pathology, 2010-02, Vol.23 (2), p.187-196</ispartof><rights>United States and Canadian Academy of Pathology, Inc. 2010</rights><rights>Copyright Nature Publishing Group Feb 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-3d49be012ab32488bc7a9363d1a345980d93f9304944ff7ed9b21ed2abb206283</citedby><cites>FETCH-LOGICAL-c503t-3d49be012ab32488bc7a9363d1a345980d93f9304944ff7ed9b21ed2abb206283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19898426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Xu-Zhi</creatorcontrib><creatorcontrib>Garcia, Marileila Varella</creatorcontrib><creatorcontrib>Li, Tian-yu</creatorcontrib><creatorcontrib>Khor, Li-Yan</creatorcontrib><creatorcontrib>Gajapathy, R Sujatha</creatorcontrib><creatorcontrib>Spittle, Cindy</creatorcontrib><creatorcontrib>Weed, Scott</creatorcontrib><creatorcontrib>Lessin, Stuart R</creatorcontrib><creatorcontrib>Wu, Hong</creatorcontrib><title>Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Cortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to study the role of cortactin in melanocytic tumor progression using immunohistochemistry on human tissues. The results reveal quantitative differences between benign and malignant lesions. Significantly higher cortactin expression is found in melanomas than in nevi (
P
<0.0001), with levels greater in metastatic than in invasive melanomas (
P
<0.05). Qualitatively, tumor tissues often show aberrant cortactin localization at the cell periphery, corresponding to its colocalization with filamentous actin in cell cortex of cultured melanoma cells. This suggests an additional level of protein dysregulation. Furthermore, in patients with metastatic disease, high-level cortactin expression correlates with poor disease-specific survival. Our data, in conjunction with outcome data on several other types of human cancers and experimental data from melanoma cell lines, supports a potential role of aberrant cortactin expression in melanoma tumor progression and a rational for targeting key elements of actin-signaling pathway for developmental therapeutics in melanomas.</description><subject>Adapter proteins</subject><subject>Automation</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cortactin - biosynthesis</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - genetics</subject><subject>Cytoskeleton - pathology</subject><subject>Disease Progression</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene amplification</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>Laboratory Medicine</subject><subject>Medicine & Public Health</subject><subject>Melanoma</subject><subject>Melanoma - genetics</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - pathology</subject><subject>Metastasis</subject><subject>Neurosciences</subject><subject>Nevus - metabolism</subject><subject>Nevus - pathology</subject><subject>Oncology</subject><subject>original-article</subject><subject>Pathology</subject><subject>Precancerous Conditions - metabolism</subject><subject>Precancerous Conditions - pathology</subject><subject>Prognosis</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Tissue Array Analysis</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kk1v1DAQhiMEokvhD3BAFge4kMUe58PmgFSt-JIqcYGz5SSTXZfEDrYD7C_p38VhoxY49GRL88zjGevNsqeMbhnl4vXouknHgxu2QKncsrK-l21YyWlOQZT3sw0VkudclnCWPQrhilJWlAIeZmdMCikKqDbZ9e4YXfiGA0ZniR4ieh2Ns4EYS0YctHWjfkN0g95rGwn-mjyGkAjietI6H3UbjX1FdOpebnljbGfsnuhOT8lGJu8iLkSCfRJGDOSniYfV3h6jaUmcR_cH3a_2x9mDXg8Bn6znefb1_bsvu4_55ecPn3YXl3lbUh5z3hWyQcpANxwKIZq21pJXvGOaF6UUtJO8l5wWsij6vsZONsCwS3gDtALBz7O3J-80NyN2Ldro9aAmb0btj8ppo_6tWHNQe_dDgYBaQpkEL1eBd99nDFGNJrQ4pN3QzUHVnEtaV5VM5Is7SWC8rlgJCXz-H3jlZm_TNygABlCzerHBCWq9C8FjfzMzo2qJh7qJh1rioVI8UtOzv7e9bVnzkAB-AkIq2T3626fv0P4GMETPMw</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Xu, Xu-Zhi</creator><creator>Garcia, Marileila Varella</creator><creator>Li, Tian-yu</creator><creator>Khor, Li-Yan</creator><creator>Gajapathy, R Sujatha</creator><creator>Spittle, Cindy</creator><creator>Weed, Scott</creator><creator>Lessin, Stuart R</creator><creator>Wu, Hong</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><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>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100201</creationdate><title>Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression</title><author>Xu, Xu-Zhi ; Garcia, Marileila Varella ; Li, Tian-yu ; Khor, Li-Yan ; Gajapathy, R Sujatha ; Spittle, Cindy ; Weed, Scott ; Lessin, Stuart R ; Wu, Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-3d49be012ab32488bc7a9363d1a345980d93f9304944ff7ed9b21ed2abb206283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adapter proteins</topic><topic>Automation</topic><topic>Biomarkers, Tumor - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Xu-Zhi</au><au>Garcia, Marileila Varella</au><au>Li, Tian-yu</au><au>Khor, Li-Yan</au><au>Gajapathy, R Sujatha</au><au>Spittle, Cindy</au><au>Weed, Scott</au><au>Lessin, Stuart R</au><au>Wu, Hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>23</volume><issue>2</issue><spage>187</spage><epage>196</epage><pages>187-196</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Cortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to study the role of cortactin in melanocytic tumor progression using immunohistochemistry on human tissues. The results reveal quantitative differences between benign and malignant lesions. Significantly higher cortactin expression is found in melanomas than in nevi (
P
<0.0001), with levels greater in metastatic than in invasive melanomas (
P
<0.05). Qualitatively, tumor tissues often show aberrant cortactin localization at the cell periphery, corresponding to its colocalization with filamentous actin in cell cortex of cultured melanoma cells. This suggests an additional level of protein dysregulation. Furthermore, in patients with metastatic disease, high-level cortactin expression correlates with poor disease-specific survival. Our data, in conjunction with outcome data on several other types of human cancers and experimental data from melanoma cell lines, supports a potential role of aberrant cortactin expression in melanoma tumor progression and a rational for targeting key elements of actin-signaling pathway for developmental therapeutics in melanomas.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>19898426</pmid><doi>10.1038/modpathol.2009.157</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adapter proteins Automation Biomarkers, Tumor - analysis Cancer Cell cycle Cortactin - biosynthesis Cytoskeleton Cytoskeleton - genetics Cytoskeleton - pathology Disease Progression Fluorescent Antibody Technique Gene amplification Humans Immunohistochemistry In Situ Hybridization, Fluorescence Kaplan-Meier Estimate Kinases Laboratory Medicine Medicine & Public Health Melanoma Melanoma - genetics Melanoma - metabolism Melanoma - pathology Metastasis Neurosciences Nevus - metabolism Nevus - pathology Oncology original-article Pathology Precancerous Conditions - metabolism Precancerous Conditions - pathology Prognosis Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - pathology Tissue Array Analysis Tumorigenesis Tumors |
| title | Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression |
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