Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and stands among the leading causes of cancer-related deaths. Although deregulation of the microbiota in the gastrointestinal tract has been frequently described in CRC, very little is known about the precise molecular mechanisms by which bacteria and their toxins modulate the process of tumorigenesis and behavior of cancer cells. In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo . To identify the mechanisms, we further investigated CCL3/CCR5 and NF-κB pathway. We found that CCL3, CCR5, NF-κB, and TRAF-6 were dramatically upregulated after rBFT1 treatment, thus suggesting that the role of rBFT1 in CRC progression may be associated with CCL3/CCR5 and NF-κB pathways. Collectively, our results indicate that rBFT1 serves as a tumor promoter and plays a crucial role in inducing the proliferation of CRC via accelerating CCL3-related molecular pathway, thus giving insights into mechanistic underpinnings for the prevention and treatment of CRC.

中文翻译：

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重组脆弱类杆菌肠毒素1（rBFT-1）通过CCL3相关分子途径促进结直肠癌的增殖

大肠癌（CRC）是世界上最常见的癌症之一，也是癌症相关死亡的主要原因之一。尽管在CRC中经常描述了胃肠道中微生物群的失调，但是对于细菌及其毒素调节肿瘤发生过程和癌细胞行为的精确分子机制知之甚少。在这项研究中，我们生产了重组脆弱类杆菌肠毒素1（rBFT1），并证明rBFT1可以促进结直肠癌细胞的细胞增殖并促进体内肿瘤的生长。为了确定机制，我们进一步研究了CCL3 / CCR5和NF-κB途径。我们发现rBFT1治疗后CCL3，CCR5，NF-κB和TRAF-6明显上调，因此提示，rBFT1在CRC进展中的作用可能与CCL3 / CCR5和NF-κB通路有关。总体而言，我们的结果表明，rBFT1充当肿瘤的启动子，并通过加速CCL3相关的分子途径在诱导CRC增殖中起关键作用，从而为预防和治疗CRC的机理基础提供了见识。