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. Inhibition of TIMP-2 using an anti-TIMP-2 antibody or ERK/MAPK inhibition by U0126 suppressed TIMP-2 mediated 5-Fu-resistance in CRC patients.

在结直肠癌患者中，使用抗timp-2抗体或者erk/mapk抑制剂u0126来抑制timp-2-erk/mapk信号通路可以抑制5-fu耐药。 结论：靶向TIMP-2-ERK/MAPK可能为攻克结直肠癌化疗中出现的5-Fu耐药提供新的治疗策略。

2022年1月12日 · 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. Inhibition of TIMP-2 using an anti-TIMP-2 antibody or ERK/MAPK inhibition by U0126 suppressed TIMP-2 mediated 5-Fu-resistance in CRC patients.

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 · 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-dependent manner.

2016年12月9日 · Here, we review how the four non-redundant tissue inhibitors of metalloproteinases (TIMPs) regulate the pericellular proteolysis of a vast range of matrix and cell surface proteins, generating...

2023年6月1日 · Inflammatory mediators IL-1β, TNF-α, and TGF-β promote TIMP-1 expression via signaling pathways, such as mitogen-activated protein kinases pathways (p38 and ERK) and TGF/SMAD pathway. TIMP-1 may involve in the pathogenesis of pulmonary diseases through the modulation of the immune response and ECM homeostasis.

2010年3月1日 · TIMP-2 binding with cell surface-associated MT1-MMP stimulates phosphorylation of MEK1/2, which is upstream of ERK1/2, and the ERK1/2 substrate p90RSK. Consistent with volumes of literature, we confirmed that the …

我们建立了一种自分泌机制，通过该机制，升高的 TIMP-2 蛋白水平通过组成性激活 ERK/MAPK 信号通路来维持结肠直肠癌细胞对 5-Fu 的抗性。 使用抗 TIMP-2 抗体抑制 TIMP-2 或通过 U0126 抑制 ERK/MAPK 可抑制 CRC 患者中 TIMP-2 介导的 5-Fu 抗性。 总之，一种新的 TIMP-2-ERK/MAPK 介导的 5-Fu 耐药机制与结直肠癌有关。 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。 5-Fluorouracil (5-Fu) is the first-line …

Analysis of the activation of cell signalling pathways demonstrated that TGF-β induced robust ERK and PI3K activation with delayed kinetics compared to the phosphorylation of Smads. The TGF-β induction of Adam12 and Timp-1 was dependent on such non-Smad signalling pathways and, importantly, HDAC inhibitors completely blocked their activation ...