| First Author | Okuma A | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 2050 |
| PubMed ID | 29234059 | Mgi Jnum | J:257682 |
| Mgi Id | MGI:6112540 | Doi | 10.1038/s41467-017-02281-x |
| Citation | Okuma A, et al. (2017) p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis. Nat Commun 8(1):2050 |
| abstractText | p16(Ink4a) and p21(Cip1/Waf1) act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16(Ink4) and p21(Cip1/Waf1), namely, tumour promotion through chemotaxis. In monocytic myeloid-derived suppressor cells (Mo-MDSCs), p16(Ink4) and p21(Cip1/Waf1) are highly expressed and stimulate CX3CR1 chemokine receptor expression by preventing CDK-mediated phosphorylation and inactivation of SMAD3. Thus, deletion of p16 (Ink4) and p21 (Cip1/Waf1) reduces CX3CR1 expression, thereby inhibiting Mo-MDSC accumulation in tumours expressing CX3CL1 and suppressing the tumour progression in mice. Notably, blockade of the CX3CL1/CX3CR1 axis suppresses tumour growth, whereas inactivation of CDKs elicits the opposite effect. These findings reveal an unexpected function of p16 (Ink4a) and p21 (Waf1/Cip1) and indicate that regulation of Mo-MDSCs chemotaxis is a valuable potential strategy for control of tumour development. |
