| Added by | mollevi |
|---|---|
| Last modified by | pcoopman |
| Group name | EquipePC |
| Item Type | Journal Article |
| Title | PKCtheta-induced phosphorylations control the ability of Fra-1 to stimulate gene expression and cancer cell migration |
| Creator | Belguise et al. |
| Author | K. Belguise |
| Author | S. Cherradi |
| Author | A. Sarr |
| Author | F. Boissiere |
| Author | N. Boulle |
| Author | J. Simony-Lafontaine |
| Author | V. Choesmel-Cadamuro |
| Author | X. Wang |
| Author | D. Chalbos |
| Abstract | The AP-1 transcription factor Fra-1 is aberrantly expressed in a large number of cancers and plays crucial roles in cancer development and progression by stimulating the expression of genes involved in these processes. However, the control of Fra-1 transactivation ability is still unclear and here we hypothesized that PKCtheta-induced phosphorylation could be necessary to obtain a fully active Fra-1 protein. Using MCF7 stable cells overexpressing equivalent levels of unphosphorylated Fra-1 or PKCtheta-phosphorylated Fra-1, we showed that PKCtheta-induced phosphorylation of Fra-1 was crucial for the stimulation of MMP1 and IL6 expression. Consistently, we found a significant positive correlation between PRKCQ (coding for PKCtheta) and MMP1 mRNA expression levels in human breast cancer samples. PKCtheta-induced phosphorylations, in part at T217 and T227 residues, strongly and specifically increased Fra-1 transcriptional activity through the stimulation of Fra-1 transactivation domain, without affecting JUN factors. More importantly, these phosphorylations were required for Fra-1-induced migration of breast cancer cells and phosphorylated Fra-1 expression was enriched at the invasion front of human breast tumors. Taken together, our findings indicate that PKCtheta-induced phosphorylation could be important for the function of Fra-1 in cancer progression. |
| Publication | Cancer Lett |
| Date | Nov 2 2016 |
| Journal Abbr | Cancer letters |
| DOI | 10.1016/j.canlet.2016.10.038 |
| ISSN | 1872-7980 (Electronic) 0304-3835 (Linking) |
| Tags | first-last-corresponding, orig, original |
| Date Added | 2018/11/14 - 12:07:50 |
| Date Modified | 2021/03/24 - 17:42:42 |
| Notes and Attachments | (Note) (Note) 27816489 (Attachment) |
Institut de Recherche en Cancérologie de
