Cell
Volume 170, Issue 3, 27 July 2017, Pages 548-563.e16
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Article
Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy

https://doi.org/10.1016/j.cell.2017.07.008Get rights and content
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Highlights

  • Specific gut microbes track with post-chemotherapy recurrence of colorectal cancer

  • F. nucleatum orchestrates the Toll-like receptor, microRNAs, and autophagy network to control cancer chemoresistance

  • Measuring and targeting F. nucleatum may be useful for patient prognosis and management

Summary

Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes.

Keywords

Colorectal cancer
recurrence
chemoresistance
F.nucleatum
autophagy
Toll-like receptor
miRNA

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