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Figures S2 and S3 from Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis

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posted on 2023-03-31, 03:21 authored by Emanuele Giurisato, Silvia Lonardi, Brian Telfer, Sarah Lussoso, Blanca Risa-Ebrí, Jingwei Zhang, Ilaria Russo, Jinhua Wang, Annalisa Santucci, Katherine G. Finegan, Nathanael S. Gray, William Vermi, Cathy Tournier

These supplementary data show that the reduction in the number of TAMs caused by myeloid ERK5 deficiency correlates with reduced melanoma cell proliferation in melanoma grafts.

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Worldwide Cancer Research

Medical Research Council Confidence in Concept

Marie Curie Research

Fondazione Beretta

Associazione Italiana per la Ricerca sul Cancro

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ARTICLE 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. These findings offer a new rationale for anti-ERK5 therapy to improve cancer patient outcomes by blocking the proliferative activity of tumor macrophages.

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    Cancer Research

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    Keywords

    Cell SignalingProtein serine-threonine kinasesDrug TargetsProtein kinase & phosphatase drug targetsImmunologyTumor-associated macrophagesPreclinical ModelsAnimal models of cancerProgression, Invasion & MetastasisInflammation and tumor developmentTumor MicroenvironmentImmune cells and the microenvironmentTumor Staging

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