TC1 (C8orf4) is involved in ERK1/2 pathway-regulated G₁- to S-phase transition

Abstract

Although previous studies have implicated a role for TC1 (C8orf4) in cancer cell proliferation, the molecular mechanism of its action is still largely unclear. In this study, we showed, for the first time, that the mRNA levels of TC1 were upregulated by mitogens (FBS/thrombin) and at least partially, through the ERK1/2 signaling pathway. Interestingly, the over-expression of TC1 promoted the G1-to S-phase transition of the cell cycle, which was delayed by the deficiency of ERK1/2 signaling in fibroblast cells. Furthermore, the luciferase reporter assay indicated that the over-expression of TC1 significantly increased Cyclin D1 promoter-driven luciferase activity. Taken together, our findings revealed that TC1 was involved in the mitogen-activated ERK1/2 signaling pathway and positively regu-

Aberrant Activation of Notch Signaling Inhibits PROX1 Activity to Enhance the Malignant Behavior of Thyroid Cancer Cells

“…In addition, PROX1 regulates several genes that were previously associated with thyroid cancer. For example, Thyroid Cancer (TC)-1 was originally isolated by its prominent expression in thyroid cancer cells (24,25) and known to promote G1/S cell cycle progression (26). While TC-1 was upregulated in PTCs, it was significantly downregulated by PROX1 re-expression (Figure 4E,F).…”

Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium

“…TC-1 is thought to competitively block interactions between β-catenin and a repressor protein, leading to upregulation of β-catenin target genes [39]. TC-1 may also play a role in NF-κB and ERK signaling pathways [40]. Downregulation TC-1 can thus lead to aberrant signaling, causing disrupted embryonic development or carcinogenesis.…”

Comprehensive proteomic and transcriptomic characterization of hepatic expression signatures affected in p14 liver conditional knockout mice

“…A study performed with A549 lung adenocarcinoma cell line exposed to hyperoxia (95% O 2 ) for 0.5–24 h demonstrated that suppression of phospho‐ERK activity by U0126 MEK inhibitor resulted in downregulation of cyclinA/B1 levels and increased the cell fraction in S phase 6. At the same time, the reduced activity of phospho‐ERK in fibroblasts results in downregulation of cyclin D1 expression and enriches cells in G1 phase 33. These data suggest that the regulation of cyclins by phospho‐ERK activity depends on the origin of the tissue.…”