TPL2 expression is correlated with distant metastasis and poor prognosis in colorectal cancer

Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells

“…MAP3K8 encodes mitogen-activated protein kinase kinase kinase 8, a member of serine/threonine kinase family (Paardekooper et al, 2018), which is involved in the MAPK/JNK/p38 and NFkB signaling pathway (Chorzalska et al, 2018). Overexpression of MAP3K8, also known as tumor progression locus 2 (TPL2), is correlated with poor prognosis and metastasis in patients with colorectal cancer (Pyo et al, 2018). Another study demonstrated that MAP3K8 induces invasion and metastasis in renal cancer cells (Liu et al, 2016).…”

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

“…Future studies should focus on exploring the mechanisms underlying the differential expression of TPL2 in various human cancers and the correlation between TPL2 expression/signaling and clinicopathological parameters in cancer patients. The TPL2 kinase was also identified as a potential predictive marker of patient responsiveness to MEK antagonist in high-grade serous ovarian carcinoma, underscoring its importance in therapy response 39 , 40 , 42 . Collectively, TPL2 signaling creates a platform to understand disease progression and the mechanism in which other anti-tumor therapies exert their effect; this knowledge can be leveraged to develop more effective and potent drugs.…”

“…However, the number of tumors with TPL2 overexpression and activation is much more significant than the subfraction of tumors with confirmed mutations, suggesting that TPL2 overexpression and activation are the main events associated with increased tumorigenesis 5 . TPL2 overexpression and increased activity are associated with poor prognosis and the progression of several human cancers including skin cancer, prostate cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, colorectal cancer, endometrial cancer, gastric cancer, EBV-related nasopharyngeal carcinoma, anaplastic large-cell lymphoma (ALCL), colitis-associated carcinoma, bladder cancer and cervical cancer (Figure 3 ) 6 , 8 , 36 , 38 - 40 . Congruently, TPL2 kinase activity has been implicated in all stages of tumorigenesis, including tumor initiation, tumor promotion and tumor progression; where it modulates cell proliferation, stem cell acquisition, angiogenesis, EMT progression, migration, invasion and metastasis 5 , 9 .…”

“…Clinical samples from cancer patients further confirm the connection between TPL2 and metastasis. TPL2 expression and activation correlate positively with distant metastasis and poor prognosis in clear cell renal cell carcinoma (ccRCC) and colorectal cancer, emphasizing the importance of TPL2 in EMT phenotype acquisition and tumor metastasis 40 , 49 .…”

“…Moreover, the clinically used anti-tumor immunotherapeutic agent IFNα is suggested to exert its anti-NF-κB and anti-COX2 effect by suppressing TPL2 activity, thereby highlighting the importance of TPL2 signaling as an anti-tumor therapeutic target 132 . Furthermore, the differential expression of TPL2 in cancer was identified as a prognosis marker in several cancers such as colorectal cancer, non-small cell lung cancer and clear cell renal cell carcinoma (ccRCC) 40 , 42 , 49 . However, there is limited data on the relationship between TPL2 expression/activity and the clinicopathological parameters.…”