Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity

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.

Preoperative C-Reactive Protein/Albumin Ratio is a Prognostic Indicator for Survival in Surgically Treated Gastrointestinal Stromal Tumors: A Retrospective Cohort Study

“…Extensive studies have shown that systemic inflammation plays an essential regulatory role in malignant tumors' occurrence and development. [30][31][32] Inflammatory factors, including acute-phase proteins such as C-reactive protein and albumin, may come from the systemic response to malignant tumors or from the secretion of malignant cells. 33 The interaction between host and tumor cells may lead to tumor progression or retraction.…”

Expression Level and Prognostic Potential of MAP3K8 in Human Cancers Based on Data Mining

“…What is the theme of this study, however, is that care has to be taken in touching on the relationships between MAP3K8 and human cancers. Although MAP3K8 was originally recognized as an oncogene since its discovery in 1991, genetic sequence analyses identi ed rare MAP3K8 mutations which is much less than altered expression and abnormal activation in human cancers [6]. Previous studies have found that overexpression and increased activation of MAP3K8 are main events associated with increased tumorigenesis including initiation, promotion and progression as well as poor prognosis [6,23].…”

“…Although MAP3K8 was originally recognized as an oncogene since its discovery in 1991, genetic sequence analyses identi ed rare MAP3K8 mutations which is much less than altered expression and abnormal activation in human cancers [6]. Previous studies have found that overexpression and increased activation of MAP3K8 are main events associated with increased tumorigenesis including initiation, promotion and progression as well as poor prognosis [6,23]. In addition, reduced MAP3K8 expression is also related to poor prognosis and tumor aggressiveness in some cancers such as non-small cell lung cancer (NSCLC) [24,25].…”

“…MAP3K8 (also called TPL2, Cot) is a MAP3K with a major role in the activation of the MAPK pathways. The encoded proteins of MAP3K8 contain a serine/threonine kinase domain, an amino-terminal region, and a carboxy-terminal tail which carries sequences important for regulation of catalytic activity of MAP3K8 [6]. Early studies identi ed the MAP3K8 gene as a proto-oncogene activated by C-terminal truncation in vivo [7].…”

C-Reactive Protein/Albumin Ratio Is a Powerful Prognostic Indicator for Survival in Surgically Resected Gastrointestinal Stromal Tumors: A Retrospective Cohort Study

“…Extensive studies have shown that systemic in ammation plays an essential regulatory role in malignant tumors' occurrence and development [24][25][26]. In ammatory factors, including acute-phase proteins such as C-reactive protein and albumin, may come from the systemic response to malignant tumors or from the secretion of malignant cells [27].…”