| Yazarlar |
Arundhati Jana
Türkiye |
|
Nancy L Krett
Türkiye |
|
Grace Guzman
Türkiye |
|
Ahmer Khalid
Türkiye |
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 |
| 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 |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | ONCOTARGET |
| Dergi ISSN | 1949-2553 |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Makale Dili | İngilizce |
| Basım Tarihi | 06-2017 |
| Cilt No | 8 |
| Sayı | 23 |
| Sayfalar | 37377 / 37393 |
| Doi Numarası | 10.18632/oncotarget.16343 |
| Makale Linki | http://www.oncotarget.com/abstract/16343 |
| Atıf Sayıları | |
| WoS | 57 |
