Propofol repressed hepatocellular carcinoma Huh-7 and HepG2 cell growth and metastasis at least by elevating DGCR5 and hereafter inactivating Raf1/ERK1/2 and Wnt/β-catenin pathways.
In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.
Analysis of patient-matched primary carcinomas and metastases showed overexpression of APC (p=0.022), MAPK3 (p=0.002) and BNIP3 (p=0.004) in the former.
NCTD inhibited MMP-9 and u-PA expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway which serves as a powerful chemopreventive agent in HCC cell metastasis.
In addition, we have demonstrated that the binding of Ang-3 to the cell surface is required for the effective inhibition of Ang-3 on tumor metastasis and that Ang-3 inhibits endothelial cell proliferation and survival and blocks Ang-1- and vascular endothelial growth factor-induced activation of extracellular signal-regulated kinase 1/2 and Akt kinases, which likely underlie the Ang-3-mediated inhibition on tumor angiogenesis and metastasis.
Biofunctional investigations revealed a tumor-suppressor role of WNK2: its inactivation led to ERK1/2 signaling activation in HCC cells, tumor-associated macrophage infiltration, and tumor growth and metastasis.
Further analysis suggested that inhibition of cell proliferation and metastasis was associated with some proteins, including p53, MMP9, Snail, CDC42, p-ERK1/2, KIF2C, KIF4A, PCNA, and Twist.
We have previously reported in a series of papers that a Kunitz-type protease inhibitor, bikunin, suppresses up-regulation of urokinase-type plasminogen activator (uPA) and its specific receptor (uPAR) expression, phosphorylation of ERK1/2 and cancer cell invasion in vitro and peritoneal disseminated metastasis in vivo.
Collectively, these data demonstrated that miR-451 is a novel prognostic biomarker for HCC patients and that function as a potential metastasis inhibitor in HCC cells through activation of the Erk1/2 signaling, at least partially by targeting c-Myc.
The subcutaneous tumors and lung metastases derived from V12S35 Ras-transformed NIH 3T3 cells expressed higher levels of activated ERK1/2 in culture when compared with the parental cellular pool before injection, indicating that selection for cells with higher levels of activated ERK1/2 occurred during tumor growth and metastasis.
These findings indicate that RON and c-Met facilitate metastasis through ERK1/2 signaling and that targeting RON and c-Met with foretinib may be an attractive therapeutic option for suppressing PCa metastasis.
In conclusion, our results demonstrate that miR-339-5p functions as a tumor suppressor and plays a role in inhibiting growth and metastasis of CRC cells through targeting PRL-1 and regulating p-ERK1/2 .These findings suggest that miR-339-5p may be useful as a new potential therapeutic target for CRC.
It also has been known to lower the phosphorylation of NF-κB and IKKα/β and reduces the metastasis as well as also lowered the ERK1/2 and PI3K activities.
We obtained further proof that PAB which could be used as a multi-targeted agent to inhibit the PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways and consequently suppress tumor growth and metastasis.
Increased semaphorin 3c expression promotes tumor growth and metastasis in pancreatic ductal adenocarcinoma by activating the ERK1/2 signaling pathway.
Mechanistic investigations suggested that DIRAS1 acted through extracellular signal-regulated kinase (ERK1/2; MAPK3/1) and p38 mitogen-activated protein kinase (MAPK; MAPK14) signaling to trigger BAD Ser112 dephosphorylation and matrix metalloproteinase (MMP)2/9 transcriptional inactivation to promote apoptosis and inhibit metastasis, respectively.
Results of the immunohistochemistry showed that the expression of ERK1/2 and p-ERK1/2 was correlated to the expression of KSR1 and p-KSR1 in the gastric cancer tissues, and the overexpression of KSR1, p-KSR1, ERK1/2 and p-ERK1/2 was significantly associated with histological grade, TNM stage, lymph node and distant metastasis.
Compared with the inhibition of ITGA6 or RPSA alone, the downregulation of both ITGA6 and RPSA weakened invasion and metastasis to a greater extent and led to the simultaneous downregulation of p-AKT and p-ERK1/2.
Polysialic acid-modified NCAM on the surface of SCLC cells is closely related to the metastatic potential of these cells; regulation of ST8SiaII may thus affect the invasiveness and metastasis of SCLC, and these processes may be associated with phosphorylation of FGFR1, ERK1/2 or MMP-9.