Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis
Background Liver metastasis is the primary cause of colorectal cancer (CRC)-associated death. Aryl-hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl-hydrocarbon receptor-mediated signalling, is overexpressed in highly metastatic human KM12SM CRC cells and other...
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| Veröffentlicht in: | British journal of cancer 2022-06, Vol.126 (11), p.1604-1615 |
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| creator | Solís-Fernández, Guillermo Montero-Calle, Ana Sánchez-Martínez, Maricruz Peláez-García, Alberto Fernández-Aceñero, María Jesús Pallarés, Pilar Alonso-Navarro, Miren Mendiola, Marta Hendrix, Jelle Hardisson, David Bartolomé, Rubén A. Hofkens, Johan Rocha, Susana Barderas, Rodrigo |
| description | Background
Liver metastasis is the primary cause of colorectal cancer (CRC)-associated death. Aryl-hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl-hydrocarbon receptor-mediated signalling, is overexpressed in highly metastatic human KM12SM CRC cells and other highly metastatic CRC cells.
Methods
Meta-analysis and immunohistochemistry were used to assess the relevance of AIP. Cellular functions and signalling mechanisms mediated by AIP were assessed by gain-of-function experiments and in vitro and in vivo experiments.
Results
A significant association of high AIP expression with poor CRC patients’ survival was observed. Gain-of-function and quantitative proteomics experiments demonstrated that AIP increased tumorigenic and metastatic properties of isogenic KM12C (poorly metastatic) and KM12SM (highly metastatic to the liver) CRC cells. AIP overexpression dysregulated epithelial-to-mesenchymal (EMT) markers and induced several transcription factors and Cadherin-17 activation. The former induced the signalling activation of AKT, SRC and JNK kinases to increase adhesion, migration and invasion of CRC cells. In vivo, AIP expressing KM12 cells induced tumour growth and liver metastasis. Furthermore, KM12C (poorly metastatic) cells ectopically expressing AIP became metastatic to the liver.
Conclusions
Our data reveal new roles for AIP in regulating proteins associated with cancer and metastasis to induce tumorigenic and metastatic properties in colon cancer cells driving liver metastasis. |
| doi_str_mv | 10.1038/s41416-022-01762-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9130499</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2668568564</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-8f098f266da47bec940f18c88421fd4329fc56c53a2b8929c7d32c9e446fb5923</originalsourceid><addsrcrecordid>eNp9Uctq3DAUFaWlmST9gS6KoGu3etmWNoUQ-oJANs1ayLLkKHgk90oemM_oH0eTmabtpiCQrs7jHjgIvaXkAyVcfsyCCto1hLGG0L5jDX2BNrTl9SFZ_xJtCCF9QxQjZ-g854c6KiL71-iMt1z0nPEN-nUF-7m534-QrIEhRQzOuqUkaEIsDowtIU54gVRcOIDTOpviMi7rNkGYXAwWmzjirSsmF1PqWMmLgxIqK3ls05yqZzEztiZaB9i6ec54hLA7WM9hV_9O8hzyJXrlzZzdm9N9ge6-fP5x_a25uf36_frqprGiF6WRnijpWdeNRvSDs0oQT6WVUjDqR8GZ8rbtbMsNG6RiyvYjZ1Y5ITo_tIrxC_Tp6Lusw9aN1sUCZtYLhK2BvU4m6H-RGO71lHZaUU6EUtXg_ckA0s_V5aIf0gqxZtY1lmwPR1QWO7IspJzB-ecNlOhDjfpYo6416qcaNa2id39ne5b87q0S-JGQKxQnB392_8f2ETnJrfg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2668568564</pqid></control><display><type>article</type><title>Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><creator>Solís-Fernández, Guillermo ; Montero-Calle, Ana ; Sánchez-Martínez, Maricruz ; Peláez-García, Alberto ; Fernández-Aceñero, María Jesús ; Pallarés, Pilar ; Alonso-Navarro, Miren ; Mendiola, Marta ; Hendrix, Jelle ; Hardisson, David ; Bartolomé, Rubén A. ; Hofkens, Johan ; Rocha, Susana ; Barderas, Rodrigo</creator><creatorcontrib>Solís-Fernández, Guillermo ; Montero-Calle, Ana ; Sánchez-Martínez, Maricruz ; Peláez-García, Alberto ; Fernández-Aceñero, María Jesús ; Pallarés, Pilar ; Alonso-Navarro, Miren ; Mendiola, Marta ; Hendrix, Jelle ; Hardisson, David ; Bartolomé, Rubén A. ; Hofkens, Johan ; Rocha, Susana ; Barderas, Rodrigo</creatorcontrib><description>Background
Liver metastasis is the primary cause of colorectal cancer (CRC)-associated death. Aryl-hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl-hydrocarbon receptor-mediated signalling, is overexpressed in highly metastatic human KM12SM CRC cells and other highly metastatic CRC cells.
Methods
Meta-analysis and immunohistochemistry were used to assess the relevance of AIP. Cellular functions and signalling mechanisms mediated by AIP were assessed by gain-of-function experiments and in vitro and in vivo experiments.
Results
A significant association of high AIP expression with poor CRC patients’ survival was observed. Gain-of-function and quantitative proteomics experiments demonstrated that AIP increased tumorigenic and metastatic properties of isogenic KM12C (poorly metastatic) and KM12SM (highly metastatic to the liver) CRC cells. AIP overexpression dysregulated epithelial-to-mesenchymal (EMT) markers and induced several transcription factors and Cadherin-17 activation. The former induced the signalling activation of AKT, SRC and JNK kinases to increase adhesion, migration and invasion of CRC cells. In vivo, AIP expressing KM12 cells induced tumour growth and liver metastasis. Furthermore, KM12C (poorly metastatic) cells ectopically expressing AIP became metastatic to the liver.
Conclusions
Our data reveal new roles for AIP in regulating proteins associated with cancer and metastasis to induce tumorigenic and metastatic properties in colon cancer cells driving liver metastasis.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-022-01762-1</identifier><identifier>PMID: 35347323</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/322 ; 692/4028/67/1504/1885 ; AKT protein ; Biomedical and Life Sciences ; Biomedicine ; Cadherins ; Cancer Research ; Carcinogenesis - genetics ; Cell Line, Tumor ; Cell Movement ; Colon cancer ; Colonic Neoplasms ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - pathology ; Drug Resistance ; Epidemiology ; Epithelial-Mesenchymal Transition ; Experiments ; Gene Expression Regulation, Neoplastic ; Hepatocytes ; Humans ; Hydrocarbons ; Immunohistochemistry ; Kinases ; Liver ; Liver cancer ; Liver Neoplasms - secondary ; Mesenchyme ; Metastases ; Metastasis ; Molecular Medicine ; Neoplasm Metastasis ; Oncology ; Proteomics ; Rectal Neoplasms ; Transcription activation ; Transcription factors ; Tumors</subject><ispartof>British journal of cancer, 2022-06, Vol.126 (11), p.1604-1615</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-8f098f266da47bec940f18c88421fd4329fc56c53a2b8929c7d32c9e446fb5923</citedby><cites>FETCH-LOGICAL-c474t-8f098f266da47bec940f18c88421fd4329fc56c53a2b8929c7d32c9e446fb5923</cites><orcidid>0000-0003-3539-7469 ; 0000-0003-1258-9396</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/PMC9130499/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130499/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35347323$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Solís-Fernández, Guillermo</creatorcontrib><creatorcontrib>Montero-Calle, Ana</creatorcontrib><creatorcontrib>Sánchez-Martínez, Maricruz</creatorcontrib><creatorcontrib>Peláez-García, Alberto</creatorcontrib><creatorcontrib>Fernández-Aceñero, María Jesús</creatorcontrib><creatorcontrib>Pallarés, Pilar</creatorcontrib><creatorcontrib>Alonso-Navarro, Miren</creatorcontrib><creatorcontrib>Mendiola, Marta</creatorcontrib><creatorcontrib>Hendrix, Jelle</creatorcontrib><creatorcontrib>Hardisson, David</creatorcontrib><creatorcontrib>Bartolomé, Rubén A.</creatorcontrib><creatorcontrib>Hofkens, Johan</creatorcontrib><creatorcontrib>Rocha, Susana</creatorcontrib><creatorcontrib>Barderas, Rodrigo</creatorcontrib><title>Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Liver metastasis is the primary cause of colorectal cancer (CRC)-associated death. Aryl-hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl-hydrocarbon receptor-mediated signalling, is overexpressed in highly metastatic human KM12SM CRC cells and other highly metastatic CRC cells.
Methods
Meta-analysis and immunohistochemistry were used to assess the relevance of AIP. Cellular functions and signalling mechanisms mediated by AIP were assessed by gain-of-function experiments and in vitro and in vivo experiments.
Results
A significant association of high AIP expression with poor CRC patients’ survival was observed. Gain-of-function and quantitative proteomics experiments demonstrated that AIP increased tumorigenic and metastatic properties of isogenic KM12C (poorly metastatic) and KM12SM (highly metastatic to the liver) CRC cells. AIP overexpression dysregulated epithelial-to-mesenchymal (EMT) markers and induced several transcription factors and Cadherin-17 activation. The former induced the signalling activation of AKT, SRC and JNK kinases to increase adhesion, migration and invasion of CRC cells. In vivo, AIP expressing KM12 cells induced tumour growth and liver metastasis. Furthermore, KM12C (poorly metastatic) cells ectopically expressing AIP became metastatic to the liver.
Conclusions
Our data reveal new roles for AIP in regulating proteins associated with cancer and metastasis to induce tumorigenic and metastatic properties in colon cancer cells driving liver metastasis.</description><subject>631/67/322</subject><subject>692/4028/67/1504/1885</subject><subject>AKT protein</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cadherins</subject><subject>Cancer Research</subject><subject>Carcinogenesis - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Experiments</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Hydrocarbons</subject><subject>Immunohistochemistry</subject><subject>Kinases</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - secondary</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Molecular Medicine</subject><subject>Neoplasm Metastasis</subject><subject>Oncology</subject><subject>Proteomics</subject><subject>Rectal Neoplasms</subject><subject>Transcription activation</subject><subject>Transcription factors</subject><subject>Tumors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9Uctq3DAUFaWlmST9gS6KoGu3etmWNoUQ-oJANs1ayLLkKHgk90oemM_oH0eTmabtpiCQrs7jHjgIvaXkAyVcfsyCCto1hLGG0L5jDX2BNrTl9SFZ_xJtCCF9QxQjZ-g854c6KiL71-iMt1z0nPEN-nUF-7m534-QrIEhRQzOuqUkaEIsDowtIU54gVRcOIDTOpviMi7rNkGYXAwWmzjirSsmF1PqWMmLgxIqK3ls05yqZzEztiZaB9i6ec54hLA7WM9hV_9O8hzyJXrlzZzdm9N9ge6-fP5x_a25uf36_frqprGiF6WRnijpWdeNRvSDs0oQT6WVUjDqR8GZ8rbtbMsNG6RiyvYjZ1Y5ITo_tIrxC_Tp6Lusw9aN1sUCZtYLhK2BvU4m6H-RGO71lHZaUU6EUtXg_ckA0s_V5aIf0gqxZtY1lmwPR1QWO7IspJzB-ecNlOhDjfpYo6416qcaNa2id39ne5b87q0S-JGQKxQnB392_8f2ETnJrfg</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Solís-Fernández, Guillermo</creator><creator>Montero-Calle, Ana</creator><creator>Sánchez-Martínez, Maricruz</creator><creator>Peláez-García, Alberto</creator><creator>Fernández-Aceñero, María Jesús</creator><creator>Pallarés, Pilar</creator><creator>Alonso-Navarro, Miren</creator><creator>Mendiola, Marta</creator><creator>Hendrix, Jelle</creator><creator>Hardisson, David</creator><creator>Bartolomé, Rubén A.</creator><creator>Hofkens, Johan</creator><creator>Rocha, Susana</creator><creator>Barderas, Rodrigo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing 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receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis</title><author>Solís-Fernández, Guillermo ; Montero-Calle, Ana ; Sánchez-Martínez, Maricruz ; Peláez-García, Alberto ; Fernández-Aceñero, María Jesús ; Pallarés, Pilar ; Alonso-Navarro, Miren ; Mendiola, Marta ; Hendrix, Jelle ; Hardisson, David ; Bartolomé, Rubén A. ; Hofkens, Johan ; Rocha, Susana ; Barderas, Rodrigo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-8f098f266da47bec940f18c88421fd4329fc56c53a2b8929c7d32c9e446fb5923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>631/67/322</topic><topic>692/4028/67/1504/1885</topic><topic>AKT protein</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cadherins</topic><topic>Cancer Research</topic><topic>Carcinogenesis - genetics</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Experiments</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Hydrocarbons</topic><topic>Immunohistochemistry</topic><topic>Kinases</topic><topic>Liver</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - secondary</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Molecular Medicine</topic><topic>Neoplasm Metastasis</topic><topic>Oncology</topic><topic>Proteomics</topic><topic>Rectal Neoplasms</topic><topic>Transcription activation</topic><topic>Transcription factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Solís-Fernández, Guillermo</creatorcontrib><creatorcontrib>Montero-Calle, Ana</creatorcontrib><creatorcontrib>Sánchez-Martínez, Maricruz</creatorcontrib><creatorcontrib>Peláez-García, Alberto</creatorcontrib><creatorcontrib>Fernández-Aceñero, María Jesús</creatorcontrib><creatorcontrib>Pallarés, Pilar</creatorcontrib><creatorcontrib>Alonso-Navarro, Miren</creatorcontrib><creatorcontrib>Mendiola, Marta</creatorcontrib><creatorcontrib>Hendrix, Jelle</creatorcontrib><creatorcontrib>Hardisson, David</creatorcontrib><creatorcontrib>Bartolomé, Rubén A.</creatorcontrib><creatorcontrib>Hofkens, Johan</creatorcontrib><creatorcontrib>Rocha, Susana</creatorcontrib><creatorcontrib>Barderas, Rodrigo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE 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Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Solís-Fernández, Guillermo</au><au>Montero-Calle, Ana</au><au>Sánchez-Martínez, Maricruz</au><au>Peláez-García, Alberto</au><au>Fernández-Aceñero, María Jesús</au><au>Pallarés, Pilar</au><au>Alonso-Navarro, Miren</au><au>Mendiola, Marta</au><au>Hendrix, Jelle</au><au>Hardisson, David</au><au>Bartolomé, Rubén A.</au><au>Hofkens, Johan</au><au>Rocha, Susana</au><au>Barderas, Rodrigo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>126</volume><issue>11</issue><spage>1604</spage><epage>1615</epage><pages>1604-1615</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
Liver metastasis is the primary cause of colorectal cancer (CRC)-associated death. Aryl-hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl-hydrocarbon receptor-mediated signalling, is overexpressed in highly metastatic human KM12SM CRC cells and other highly metastatic CRC cells.
Methods
Meta-analysis and immunohistochemistry were used to assess the relevance of AIP. Cellular functions and signalling mechanisms mediated by AIP were assessed by gain-of-function experiments and in vitro and in vivo experiments.
Results
A significant association of high AIP expression with poor CRC patients’ survival was observed. Gain-of-function and quantitative proteomics experiments demonstrated that AIP increased tumorigenic and metastatic properties of isogenic KM12C (poorly metastatic) and KM12SM (highly metastatic to the liver) CRC cells. AIP overexpression dysregulated epithelial-to-mesenchymal (EMT) markers and induced several transcription factors and Cadherin-17 activation. The former induced the signalling activation of AKT, SRC and JNK kinases to increase adhesion, migration and invasion of CRC cells. In vivo, AIP expressing KM12 cells induced tumour growth and liver metastasis. Furthermore, KM12C (poorly metastatic) cells ectopically expressing AIP became metastatic to the liver.
Conclusions
Our data reveal new roles for AIP in regulating proteins associated with cancer and metastasis to induce tumorigenic and metastatic properties in colon cancer cells driving liver metastasis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>35347323</pmid><doi>10.1038/s41416-022-01762-1</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-3539-7469</orcidid><orcidid>https://orcid.org/0000-0003-1258-9396</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2022-06, Vol.126 (11), p.1604-1615 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | 631/67/322 692/4028/67/1504/1885 AKT protein Biomedical and Life Sciences Biomedicine Cadherins Cancer Research Carcinogenesis - genetics Cell Line, Tumor Cell Movement Colon cancer Colonic Neoplasms Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - pathology Drug Resistance Epidemiology Epithelial-Mesenchymal Transition Experiments Gene Expression Regulation, Neoplastic Hepatocytes Humans Hydrocarbons Immunohistochemistry Kinases Liver Liver cancer Liver Neoplasms - secondary Mesenchyme Metastases Metastasis Molecular Medicine Neoplasm Metastasis Oncology Proteomics Rectal Neoplasms Transcription activation Transcription factors Tumors |
| title | Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis |
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