RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma.

Abstract

Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor-associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP-1 cells, promoted M2-like macrophage polarization in vitro, and increased the proportion of M2-like macrophages in a xenograft mouse model. Moreover, both M1- and M2-like macrophage polarization-associated proteins were induced in macrophages cocultured with RACK1-silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C-C motif chemokine 2 (CCL2), C-C motif chemokine 5 (CCL5), interleukin-6 (IL-6), and interleukin-1 (IL-1) are closely related to RACK1 expression. In addition, blocking nuclear factor-kappa B (NF-κB) could promote M2-like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2-like polarization by regulating NF-κB and could be used as a potential therapeutic target for antitumor immunity.

• Authors: Hongxia Dan, Sai Liu, Jiajia Liu, Dongjuan Liu, Fengying Yin, Zihao Wei, Jiongke Wang, Yu Zhou, Lu Jiang, Ning Ji, Xin Zeng, Jing Li, Qianming Chen
• Journal: Molecular oncology (Mol Oncol) Vol. 14 Issue 4 Pg. 795-807 (04 2020) ISSN: 1878-0261 [Electronic] United States
• PMID: 31997535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Chemical References

• NF-kappa B
• Neoplasm Proteins
• RACK1 protein, human
• Receptors for Activated C Kinase

Topics

• Animals
• Cell Line, Tumor
• Disease Progression
• Female
• Head and Neck Neoplasms (diagnosis, immunology, pathology)
• Humans
• Macrophage Activation
• Macrophages (immunology, pathology)
• Male
• Mice, Inbred BALB C
• Middle Aged
• NF-kappa B (immunology)
• Neoplasm Proteins (immunology)
• Prognosis
• Receptors for Activated C Kinase (immunology)
• Signal Transduction
• Squamous Cell Carcinoma of Head and Neck (diagnosis, immunology, pathology)