To further determine that U0126 can reverse TIMP-2-induced 5-Fu resistance in CRC through the ERK/MAPK signaling pathway, we downregulated ERK/MAPK in DLD-1 5-FuS and HCT116 5-FuS cells using U0126. Then, cells were treated with recombinant TIMP-2, followed by increasing the concentrations of 5-Fu in the culture ( Figure 7C and 7D ).

2022年1月12日 · In a 5-Fu-resistant patient-derived xenograft (PDX) model, TIMP-2 was also found to be highly expressed. We established an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway.

目的：5-氟尿嘧啶（5-fu）是治疗结直肠癌的一线化疗药物。然而，长时间使用5-氟尿嘧啶会导致化疗患者对该药物耐受而不能充分发挥其抗肿瘤作用。细胞因子在肿瘤耐药中扮演着重要的作用，而它们大部分的机制都还是未知的。大量文献显示，细胞因子timp-2与结直肠癌患者的预后密切 …

Recently, D’Alessio et al. have suggested that the effect of TIMP-2 on cell growth is mediated through its binding to MMP-14 on the cell surface and subsequent extracellular regulated kinase (ERK)1/2 activation. Since a TIMP-2 mutant with an extra alanine added to the N-terminus (Ala+TIMP-2), which does not bind to the active site of MMP-14 ...

2025年1月18日 · Single-cell RNA sequencing identified a subset of ERK active DUSP2 low cells continuing to expand from early to advanced stage PDAC. In vitro and in vivo studies reveal that early infiltrating macrophage-derived tissue inhibitor of metallopeptidase 1 (TIMP-1) is the key factor in maintaining the ERK active DUSP2 low cell population in a CD63 ...

2016年12月9日 · TIMPs are proteins of 184–194 amino acids and ∼ 21 kDa in molecular weight 5 ().They are ∼ 40% identical in amino acid sequence, with TIMP2 and TIMP4 sharing most similarities with one ...

因此，靶向 timp-2 或 erk/mapk 可能为克服结直肠癌化疗中的 5-fu 耐药提供新策略。 "点击查看英文标题和摘要" TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer 5-Fluorouracil (5-Fu) is the first-line chemotherapeutic option for …

2010年3月1日 · The TIMP-2/MT1-MMP-mediated signal generated a significant (2- to 3-fold) increase in the levels of pMEK/ pERK in the cells, thus suggesting the primary role of the TIMP-2/MT1-MMP interactions in the activation of ERK. TIMP-2 did not induce the ERK/MEK pathway in the cells which exhibited a low level of MT1-MMP (e.g., MT1-MMP-deficient breast ...

2006年9月29日 · To search for the signaling critical for the Con A-dependent TIMP-2 production, we next examined the Con A-dependent activation of Erk and p38 MAP kinase by use of antibody specific for their phosphorylated forms (Fig. 2, Fig. 3).As we previously reported [14], phosphorylation of Erk was increased by Con A-treatment in wild-type cells.In contrast, Con A-dependent phosphorylation of Erk was ...

2022年1月12日 · Therefore, targeting TIMP-2 or ERK/MAPK may provide a new strategy to overcome 5-Fu resistance in colorectal cancer chemotherapy. TIMP-2 is elevated in 5-Fu resistant CRC patients and predicts ...