Khan Shahanavaj
Nanomedicine & Biotechnology Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Crit Rev Oncol Hematol. 2015 Dec;96(3):475-82. doi: 10.1016/j.critrevonc.2015.05.002. Epub 2015 May 15.
The epithelium of gastrointestinal tract organizes many innate defense systems against microbial intruders such as integrity of epithelial, rapid eviction of infected cells, quick turnover of epithelial cell, intrinsic immune responses and autophagy. However, Enteropathogenic Escherichia coli (EPEC) are equipped with well developed infectious tricks that evade the host defense systems and utilize the gastrointestinal epithelium as a multiplicative foothold. During multiplication on and within the epithelium, EPEC secrete various toxins that can weaken, usurp, and use many host cellular systems. However, the possible mechanisms of pathogenesis are still poorly elusive. Recent study reveals the existence of EPEC in colorectal cancer patients and their potential role in depletion of DNA mismatch repair (MMR) proteins of host cell in colonic cell lines. The EPEC colonised intracellularly in colon mucosa of colorectal carcinoma whereas extracellular strain was detected in mucosa of normal colon cells. Interestingly, alteration in MutS, MutL complexes and MUTYH of mammalian cells may be involved in development of CRC. These data propose that MMR of E. coli may be potential therapeutic targets and early detection biomarkers for CRC. This article reviews the potential role of E. coli MutS, MutL and MutY protein in CRC aetiology.
胃肠道上皮组织构建了许多针对微生物入侵者的固有防御系统，如上皮的完整性、受感染细胞的快速清除、上皮细胞的快速更新、固有免疫反应和自噬。然而，肠致病性大肠杆菌（EPEC）具备完善的感染策略，可逃避宿主防御系统，并将胃肠道上皮作为繁殖据点。在上皮表面及上皮内繁殖期间，EPEC分泌多种毒素，这些毒素可削弱、篡夺并利用许多宿主细胞系统。然而，其发病机制仍知之甚少。最近的研究揭示了结直肠癌患者中存在EPEC，以及它们在结肠细胞系中耗尽宿主细胞DNA错配修复（MMR）蛋白方面的潜在作用。EPEC在结直肠癌的结肠黏膜内定殖，而在正常结肠细胞的黏膜中检测到细胞外菌株。有趣的是，哺乳动物细胞中MutS、MutL复合物和MUTYH的改变可能与结直肠癌的发生有关。这些数据表明，大肠杆菌的MMR可能是结直肠癌潜在的治疗靶点和早期检测生物标志物。本文综述了大肠杆菌MutS、MutL和MutY蛋白在结直肠癌病因学中的潜在作用。
