Abstract 5090: α1β1 is pro-proliferative and promigratory integrin and its expression is upregulated by the MYC oncogenic factor in colorectal cancer
Notice bibliographique
Résumé
Abstract Background Colorectal cancer (CRC) is a multi-step process that involves successive mutation, epigenetic alteration and gene dysregulation. Integrins are a family of heterodimeric glycoproteins involved in bidirectional cell signaling and participate in the regulation of cell shape, adhesion, migration, survival and proliferation. The integrin α1 subunit is known to be involved in RAS/ERK proliferative pathway activation and plays an important role in mammary carcinoma cell proliferation and migration. In the small intestine, α1 is present in the crypt proliferative compartment and absent in the villus. In mouse models, the α1β1 integrin, together with the Kras oncogenic factor, potentiates tumor growth. Very little is known about α1β1 function in CRC. Aims: As we have recently shown that α1 is present in 65% of CRC (Boudjadi et al, 2013), that its expression is controlled by the MYC oncogenic factor and that the expressions of α1 and MYC correlate in 72.3% of colon adenocarcinomas (Boudjadi et al, Oncogene 2015) we postulated that integrin α1β1 has a pro-tumoral contribution to CRC related to α1 function. METHODS: α1β1 function was studied in HT29, T84 and SW480 CRC cell lines using shRNA silencing targeting α1 (shα1) compared to an shRNA control (shCtrl). Cell proliferation was assessed by cell count and BrdU incorporation. Migration was tested by the scratch test assay. For the anoikis test, cells were kept in suspension without serum for 24 hours on poly-2-hydroxyethyl methacrylate (polyHEMA)-coated dishes and were then lysed and subjected to caspase3 activity measurement and cleaved PARP expression. To test tumorigenic capacity, shα1 and shCtrl HT29 cells were injected into the dorsal subcutaneous tissue of female CD1 nu/nu mice. The tumor volume was assessed by external measurement. After resection, α1 knockdown was confirmed at the mRNA and protein levels. RESULTS: In HT29, T84 and SW480 cells, α1 mRNA silencing resulted in reduced cell growth and proliferation compared to the control. Caspase3 activity measurement and cleaved PARP expression in HT29 and T84 cells showed that resistance to anoikis was altered in shα1 cells compared to shCtrl. Wound healing was delayed in shα1 HT29 and T84 cells compared to shCtrl. Moreover, tumor development in xenografts was reduced in HT29 shα1 cells. Histopathological analysis showed extensive necrosis areas and low mitotic index in shα1 tumors compared to the shCtrl tumors. CONCLUSION: Our results show that α1β1 is involved in tumor cell proliferation, survival and migration. This finding suggests that α1β1 is involved in colorectal cancer progression. (Supported by the CIHR) Citation Format: Salah Boudjadi, Gérald Bernatchez, Blanche Sénicourt, Marco Beausejour, Pierre-Henri Vachon, Julie Carrier, Jean-Francois Beaulieu. α1β1 is pro-proliferative and promigratory integrin and its expression is upregulated by the MYC oncogenic factor in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5090.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».