ABSTRACT
Over the years, tumor progression locus 2 (TPL2) has been identified as an essential modulator of immune responses that conveys inflammatory signals to downstream effectors, subsequently modulating the generation and function of inflammatory cells. TPL2 is also differentially expressed and activated in several cancers, where it is associated with increased inflammation, malignant transformation, angiogenesis, metastasis, poor prognosis and therapy resistance. However, the relationship between TPL2-driven inflammation, tumorigenesis and tumor immunity has not been addressed. Here, we reconcile the function of TPL2-driven inflammation to oncogenic functions such as inflammation, proliferation, apoptosis resistance, angiogenesis, metastasis, immunosuppression and immune evasion. We also address the controversies reported on TPL2 function in tumor-promoting inflammation and tumorigenesis, and highlight the potential role of the TPL2 adaptor function in regulating the mechanisms leading to pro-tumorigenic inflammation and tumor progression. We discuss the therapeutic implications and limitations of targeting TPL2 for cancer treatment. The ideas presented here provide some new insight into cancer pathophysiology that might contribute to the development of more integrative and specific anti-inflammatory and anti-cancer therapeutics.
Subject(s)
MAP Kinase Kinase Kinases/metabolism , Neoplasms/immunology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins/metabolism , Animals , Apoptosis/genetics , Apoptosis/immunology , Carcinogenesis/drug effects , Carcinogenesis/genetics , Carcinogenesis/immunology , Cell Proliferation/genetics , Disease Models, Animal , Disease Progression , Humans , Inflammation/drug therapy , Inflammation/genetics , Inflammation/immunology , Inflammation/pathology , MAP Kinase Kinase Kinases/antagonists & inhibitors , MAP Kinase Kinase Kinases/genetics , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , MAP Kinase Signaling System/immunology , Mice , Mice, Knockout , Molecular Targeted Therapy/methods , Mutation , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/genetics , Tumor Escape/drug effects , Tumor Escape/geneticsABSTRACT
Mechano growth factor (MGF) is an autocrine/paracrine factor and sensitive to mechanical stimulation. MGF can be highly expressed in various soft tissues under physical stimuli, biochemistry stimuli or in damaged situation. MGF may "compensate" the stress for tissue in the processing of tissue repair. MGF can effectively accelerate the repair of the soft tissue by promoting the proliferation, migration and differentiation of cells. This paper summarizes the MGF expressions in different soft tissues and their functions in soft tissue repair. The paper also discusses current problems and challenges in using MGF to repair the soft tissue.
