Giurisato, E, Lonardi, S, Telfer, B, Lussoso, S, Risa-Ebrí, B, Zhang, J, Russo, I ORCID: https://orcid.org/0000-0002-2269-7078, Wang, J, Santucci, A, Finegan, KG, Gray, NS, Vermi, W and Tournier, C (2020) Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis. Cancer Research, 80 (16). 3319 - 3330.

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Abstract

The presence of immunosuppressive macrophages that become activated in the tumor microenvironment constitutes a major factor responsible for tumor growth and malignancy. In line with this knowledge, we report here that macrophage proliferation is a significant feature of advanced stages of cancer. Moreover, we have found that a high proportion of proliferating macrophages in human tumors express ERK5. ERK5 was required for supporting the proliferation of macrophages in tumor grafts in mice. Furthermore, myeloid ERK5 deficiency negatively impacted the proliferation of both resident and infiltrated macrophages in metastatic lung nodules. ERK5 maintained the capacity of macrophages to proliferate by suppressing p21 expression to halt their differentiation program. Collectively, these data provide insight into the mechanism underpinning macrophage proliferation to support malignant tumor development, thereby strengthening the value of ERK5-targeted therapies to restore antitumor immunity through the blockade of protumorigenic macrophage activation.

Item Type: Article
Additional Information: The final version of this accepted manuscript and all relevant information related to it, including copyrights, can be found online at; https://cancerres.aacrjournals.org/content/80/16/3319
Subjects: R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Depositing User: Symplectic
Date Deposited: 02 Aug 2021 15:45
Last Modified: 02 Aug 2021 15:45
URI: https://eprints.keele.ac.uk/id/eprint/9843

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