Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy. Cell. 2017, 170(3):548-563.e16.

報告日期: 2017/10/31
報告時間: 15:10/16:00
報告學生: 王孝瑄
講評老師: 張雋曦
附件下載: 下載[1664-1506044932-1.pdf] 

Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy

Cell , Volume 170 , Issue 3 , p548–563.e16 , 27 July 2017

Presenter : Hsiao - Hsuan Wang                        Date : 2017/10/31 (Tue.) 15:10-16:00

Commentator : Dr. Chun Hei Antonio Cheung     Location : Room 602, Med, Collage Building

Abstract:

 

 

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. The chemotherapeutic agents, such as 5-fluorouracil (5-FU) and Oxaliplatin, are widely used in the treatment of advanced CRC patients. However, almost half of the patients who initially responded to these drugs eventually experienced tumor recurrence [1]. Thus, elucidating the mechanism of CRC chemoresistance is essential. During the past decades, several mechanisms acquired by cancer have been described. For example, the enhancement of drug efflux, DNA repair proficiency, and cell survival ability (likes autophagy) [2].Recently, it has been proposed that the gut microbiota may also affect chemotherapy [3]. Furthermore, several groups showed that the abundance of F. nucleatum is increased in CRC carcinogenesis [4]. However, the potential effect of F. nucleatum on CRC chemotherapy is unknown. Here, the authors wonder whether the specific gut microbiota - F. nucleatumaffect the efficacy of CRC chemotherapy.By using 16s rRNA sequencing, the authors found that F. nucleatum is enriched in recurrent CRC compared to non-recurrent CRC patients. Also, the amount of F. nucleatum is associated with patient outcome. After co-cultured with F. nucleatum, CRC cellsshowed enrichment of genes involved in autophagy, like ULK1 and ATG7. Both in vitro and in vivo, F. nucleatum mechanistically activated the TLR4/MYD88 innate immune pathway, resulting in the selective loss of miR-18a* and miR-4802, the increase of ULK1 and ATG7 gene expression and caused chemoresistance finally. Consistent with these findings, the enriched amount of F. nucleatum, the loss of specific microRNA and the increased ATGs expression are clinically relevant in recurrent CRC patients. Collectively, these findings indicate that specific gut microbiota plays a critical role in mediating CRC chemoresistance. Detecting or targeting F. nucleatum may be useful for CRC prognosis and treatment in the future.

References:

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  4. Castellarin M, Warren R, Holt RA. et al. F. nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306.