Expression of phosphorylated extracellular signal-regulated kinase at the invasive front of hepatic colorectal metastasis

Abstract

Raf-1 kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, suppresses metastasis in a number of cancer types, including colorectal carcinoma (CRC); thus, RKIP downregulation significantly contributes to CRC invasiveness and metastatic potential. However, our previous study demonstrated that RKIP-positive tumors in CRC patients are predictive of hepatic colorectal metastases (HCMs). Based on the previous finding that the ERK pathway can be activated independently of RKIP, we hypothesized that RKIP-expressing HCMs may express significant levels of phosphorylated ERK (pERK). Thus, the present study evaluated the expression of RKIP and pERK in 68 HCM tissue samples using immunohistochemistry. RKIP expression was positive in 22 (32.4%) of the 68 samples, seven (31.8%) of which exhibited nuclear pERK immunoreactivity exclusively at the invasive tumor front. Furthermore, pERK expression at the invasive front was significantly associated with recurrent HCM following hepatic resection, and pERK expression observed at the invasive front of RKIP-expressing HCMs indicated that the activation of the ERK pathway may also be involved in the invasive process of these tumors, despite the presence of RKIP. A strong association between pERK expression and the presence of recurrent HCM may indicate that the ERK pathway is important in the metastatic recurrence of RKIP-positive HCM.

Knockdown of linc-POU3F3 suppresses the proliferation, apoptosis, and migration resistance of colorectal cancer

“…Various factors may influence metastatic ability of cancer cells through different signaling pathways [ 39 , 40 ]. SMAD4, as a major factor of the BMP pathway, participates in variety physiological and pathological processes, including metastasis [ 41 , 42 ].…”

Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma

“…OPG protein expression was assessed by immunohistochemistry using the Bond Polymer Intense Detection System (Vision Bio-Systems, Mount Waverley, Victoria, Australia), following the manufacturer's instructions. The general procedure has been described [ 23 – 28 ]: 4-μm sections of formalin-fixed, paraffin-embedded tissue were deparaffinized with Bond Dewax Solution (Vision BioSystems), and an antigen retrieval procedure was performed using Bond ER Solution (Vision BioSystems) for 30 min at 100°C. Endogenous peroxidases were quenched with hydrogen peroxide for 5 min.…”

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

“…Currently, it is believed that therapy resistance is the consequence of a clone selection during therapy and the presence/generation of novel mutations in cancer cells that enable them to resist the cytotoxic attack [ 120 ]. Kim et al have shown that CRC seems to follow the clonal evolution concept [ 121 ]. In this model, the gradual gain of mutations or non-genetic alterations leads to the development of specific sub-clones with different abilities to adapt to the tumor microenvironment, resulting in inter- and intra-tumoral heterogeneity [ 33 ].…”