NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway
Yazarlar (11)
Arundhati Jana
Türkiye
Nancy L Krett
Türkiye
Grace Guzman
Türkiye
Ahmer Khalid
Türkiye
Prof. Dr. Özkan ÖZDEN
Kafkas Üniversitesi, Türkiye
Jonas J Staudacher
Türkiye
Jessica Bauer
Türkiye
Seung Hyun Baik
Türkiye
Timothy Carroll
Türkiye
Cemal Yazici
Türkiye
Barbara Jung
Türkiye
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
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| Dergi Adı | ONCOTARGET | ||
| Dergi ISSN | 1949-2553 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | İngilizce | Basım Tarihi | 06-2017 |
| Cilt / Sayı / Sayfa | 8 / 23 / 37377–37393 | DOI | 10.18632/oncotarget.16343 |
| Makale Linki | http://www.oncotarget.com/abstract/16343 | ||
| Özet |
| Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation. We hypothesize that activation of the E3 ubiquitin ligase MDM2 by NFkB leads to p21 degradation in response to activin treatment. To dissect the link between activin and pro-carcinogenic NFkB signaling and downstream targets, we found that activin but not TGFB induced activation of NFkB leading to increased MDM2 ubiquitin ligase via PI3K. Further, overexpression of wild type p65 NFkB increased MDM2 expression while the NFkB inhibitors NEMO-binding domain (NBD) and Bay11-7082 blocked the activin-induced increase in MDM2. In conclusion, in colon cancer cell migration, activin utilizes NFkB to induce MDM2 activity leading to the degradation of p21 in a PI3K dependent mechanism. This provides new mechanistic knowledge linking activin and NFkB signaling in advanced colon cancer which is applicable to targeted therapeutic interventions. |
| Anahtar Kelimeler |
| activin | NF kappa B | colon cancer | MDM2 | migration |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 65 |