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Title: | Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis | Authors: | Solis-Fernandez, Guillermo Montero-Calle, Ana Sanchez-Martinez, Maricruz Pelaez-Garcia, Alberto Jesus Fernandez-Acenero, Maria Pallares, Pilar Alonso-Navarro, Miren Mendiola, Marta HENDRIX, Jelle Hardisson, David Bartolome, Ruben A. Hofkens, Johan Rocha, Susana Barderas, Rodrigo |
Issue Date: | 2022 | Publisher: | SPRINGERNATURE | Source: | BRITISH JOURNAL OF CANCER | Status: | Early view | 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. | Notes: | Barderas, R (corresponding author), Inst Salud Carlos III, Chron Dis Programme UFIEC, E-28220 Madrid, Spain.; Rocha, S (corresponding author), Katholieke Univ Leuven, Mol Imaging & Photon Div, Chem Dept, Fac Sci, Celestijnenlaan 200F, B-3001 Leuven, Belgium. susana.rocha@kuleuven.be; r.barderasm@isciii.es |
Document URI: | http://hdl.handle.net/1942/37238 | ISSN: | 0007-0920 | e-ISSN: | 1532-1827 | DOI: | 10.1038/s41416-022-01762-1 | ISI #: | WOS:000773846700001 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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s41416-022-01762-1.pdf Restricted Access | Published version | 2.52 MB | Adobe PDF | View/Open Request a copy |
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