Fusobacterium nucleatum Promotes Metastasis in Colorectal Cancer by Activating Autophagy Signaling via the Upregulation of CARD3 Expression

: We aimed to measure the abundance of ( ) in colorectal cancer (CRC) tissues from patients and to uncover the function of this bacterium in colorectal tumor metastasis. : We collected metastatic and non-metastatic CRC tissues to analyze abundance. Cells were incubated with or chloroquine (CQ) or we...

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Veröffentlicht in:Theranostics 2020, Vol.10 (1), p.323-339
Hauptverfasser: Chen, Yongyu, Chen, Yan, Zhang, Jixiang, Cao, Pan, Su, Wenhao, Deng, Yunchao, Zhan, Na, Fu, Xiangsheng, Huang, Yun, Dong, Weiguo
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Sprache:eng
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Zusammenfassung:: We aimed to measure the abundance of ( ) in colorectal cancer (CRC) tissues from patients and to uncover the function of this bacterium in colorectal tumor metastasis. : We collected metastatic and non-metastatic CRC tissues to analyze abundance. Cells were incubated with or chloroquine (CQ) or were transfected with CARD3-targeting siRNA; the expression of mRNAs and proteins was then measured. CRC cells stably transfected with shRNA-luc were mixed with and intravenously injected into BALB/cJ mice. APC , CARD3 and CARD3 C57BL mice were given ; some mice were given azoxymethane (AOM) and dextran sodium sulfate (DSS). : was abundant in CRC tissues from patients with metastasis. infection increased CRC cell motility and upregulated the expression of CARD3, LC3-II, Beclin1 and Vimentin, and downregulated the expression of E-cadherin and P62 in CRC cells. These effects were attenuated by treatment with CQ, siCARD3 or both. APC mice gavaged with developed more aggressive tumors than control mice. After AOM/DSS administration, the colorectums of CARD3 mice had fewer tumors than those of control mice. Tumors from CARD3 mice had lower levels of LC3-II and Beclin1 and higher levels of P62 than those from control mice. BALB/cJ mice injected with both CT26-luc cells and formed more metastases than control mice. CQ treatment, CARD3 knockdown or both reduced the ability of CT26-luc cells to form metastases . : is enriched in CRC tissues from patients with metastasis. orchestrates CARD3 and autophagy to control CRC metastasis. Measuring and targeting and its associated pathways will yield approaches for the prevention and treatment of CRC metastasis.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.38870