Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Cancer Sci. 2013 Sep;104(9):1139-45. doi: 10.1111/cas.12205. Epub 2013 Jun 24.
Inflammation-associated malignancies of the gastrointestinal tract (GI), including those of the stomach and colon, collectively rank as the highest cause of cancer-related deaths worldwide. It has been well documented that the deregulated activation of the archetypal pro-inflammatory and oncogenic transcription factors nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription (STAT)3 is a common feature of GI cancers that invariably correlates with poor prognosis. Signal transducer and activator of transcription 3 and NF-κB are key downstream signal transducers of the interleukin (IL)-6 cytokine and toll-like receptor (TLR) families, respectively, and until recently, the potential involvement of these two families in the pathogenesis of cancer has been investigated in isolation. However, there is now emerging evidence of the complex interplay between the IL-6 cytokine and TLR families in GI tract cancers, with a surprising twist in the identification of a non-immune role for specific TLR family members. In this review, we discuss the molecular mechanisms associated with cross-talk between the IL-6 cytokine family/STAT3 signaling network and the TLR family/NF-κB signaling network, and we address the potential benefit of their therapeutic targeting in gastric and colorectal cancers.
炎症相关的胃肠道（GI）恶性肿瘤，包括胃癌和结肠癌，是全球癌症相关死亡的主要原因。有充分的证据表明，典型的促炎和致癌转录因子核因子-κB（NF-κB）和信号转导子和转录激活子（STAT）3 的失调激活是 GI 癌症的共同特征，不可避免地与预后不良相关。STAT3 和 NF-κB 分别是白细胞介素（IL）-6 细胞因子和 Toll 样受体（TLR）家族的关键下游信号转导子，直到最近，这两个家族在癌症发病机制中的潜在作用才被单独研究。然而，现在有越来越多的证据表明，IL-6 细胞因子家族/TLR 家族在胃肠道癌症中存在复杂的相互作用，并且在鉴定特定 TLR 家族成员的非免疫作用方面出现了令人惊讶的转折。在这篇综述中，我们讨论了与 IL-6 细胞因子家族/STAT3 信号网络和 TLR 家族/NF-κB 信号网络之间的串扰相关的分子机制，并探讨了它们在胃癌和结直肠癌治疗中的潜在益处。
