| First Author | Petrenko O | Year | 2021 |
| Journal | PLoS One | Volume | 16 |
| Issue | 3 | Pages | e0247394 |
| PubMed ID | 33651821 | Mgi Jnum | J:305178 |
| Mgi Id | MGI:6510484 | Doi | 10.1371/journal.pone.0247394 |
| Citation | Petrenko O, et al. (2021) IL-6 promotes MYC-induced B cell lymphomagenesis independent of STAT3. PLoS One 16(3):e0247394 |
| abstractText | The inflammatory cytokine IL-6 is known to play a causal role in the promotion of cancer, although the underlying mechanisms remain to be completely understood. Interplay between endogenous and environmental cues determines the fate of cancer development. The Emu-myc transgenic mouse expresses elevated levels of c-Myc in the B cell lineage and develops B cell lymphomas with associated mutations in p53 or other genes linked to apoptosis. We generated Emu-myc mice that either lacked the IL-6 gene, or lacked the STAT3 gene specifically in B cells to determine the role of the IL-6/JAK/STAT3 pathway in tumor development. Using the Emu-myc lymphoma mouse model, we demonstrate that IL-6 is a critical tumor promoter during early stages of B cell lymphomagenesis. IL-6 is shown to inhibit the expression of tumor suppressors, notably BIM and PTEN, and this may contribute to advancing MYC-driven B cell tumorigenesis. Several miRNAs known to target BIM and PTEN are upregulated by IL-6 and likely lead to the stable suppression of pro-apoptotic pathways early during the tumorigenic process. STAT3, a classical downstream effector of IL-6, appears dispensable for Emu-myc driven lymphomagenesis. We conclude that the growth-promoting and anti-apoptotic mechanisms activated by IL-6 are critically involved in Emu-myc driven tumor initiation and progression, but the B cell intrinsic expression of STAT3 is not required. |
