Campylobacter jejuni-derived cytolethal distending toxin colorectal cancer metastasis

被引：0

作者：

He, Zhen ^{[1
,2
,3
]}

Yu, Jing ^{[1
,2
,3
,4
]}

Gong, Junli ^{[1
,2
,3
,4
]}

Wu, Jinjie ^{[1
,2
,4
]}

Zong, Xuan ^{[5
]}

Luo, Zhanhao ^{[2
]}

He, Xiaowen ^{[1
]}

Cheng, Wai Ming ^{[2
]}

Liu, Yugeng ^{[6
]}

Liu, Chen ^{[1
,2
]}

Zhang, Qiang ^{[7
]}

Dai, Lei ^{[6
]}

Ding, Tao ^{[8
]}

Gao, Beile ^{[9
]}

Gharaibeh, Raad Z. ^{[11
,12
]}

Huang, Jinlin ^{[10
]}

Jobin, Christian ^{[11
,13
]}

Lan, Ping ^{[1
,2
,3
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Gen Surg, Guangzhou 510655, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Prov Key Lab Colorectal & Pelv Floor Dis, Guangzhou 510655, Guangdong, Peoples R China

[3] Sun Yat sen Univ, Affiliated Hosp 6, Biomed Innovat Ctr, Guangzhou 510655, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Key Lab Human Microbiome & Chron Dis, Minist Educ, Guangzhou 510655, Guangdong, Peoples R China

[5] Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Jiangsu Key Lab Zoonosis, Yangzhou, Jiangsu, Peoples R China

[6] Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol SIAT, CAS Key Lab Quantitat Engn Biol, Shenzhen 518055, Guangdong, Peoples R China

[7] Sun Yat Sen Univ, Sch Med, Guangzhou 510655, Guangdong, Peoples R China

[8] Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China

[9] Chinese Acad Sci, South China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, CAS Key Lab Trop Marine Bio Resources & Ecol, Guangzhou 510301, Guangdong, Peoples R China

[10] Ocean Univ China, Key Lab Aquaculture Nutr & Feed, Key Lab Mariculture, Qingdao 266003, Shandong, Peoples R China

[11] Univ Florida, Dept Med, Div Gastroenterol, Gainesville, FL 32610 USA

[12] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA

[13] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL 32610 USA

来源：

CELL HOST & MICROBE | 2024年 / 32卷 / 12期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

LIVER METASTASES; ADENOCARCINOMA; IDENTIFICATION; MICROBIOME; BACTERIA; TUMOR;

D O I：

10.1016/j.chom.2024.11.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (DcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.

引用

页码：2080 / 2091.e6

页数：19

共 55 条

[1] Mantke R., Schmidt U., Wolff S., Kube R., Lippert H., Incidence of synchronous liver metastases in patients with colorectal cancer in relationship to clinico-pathologic characteristics. Results of a German prospective multicentre observational study, Eur. J. Surg. Oncol., 38, pp. 259-265, (2012)
[2] Elferink M.A.G., de Jong K.P., Klaase J.M., Siemerink E.J., de Wilt J.H.W., Metachronous metastases from colorectal cancer: a population-based study in North-East Netherlands, Int. J. Colorectal Dis., 30, pp. 205-212, (2015)
[3] Rahbari N.N., Carr P.R., Jansen L., Chang-Claude J., Weitz J., Hoffmeister M., Brenner H., Time of metastasis and outcome in colorectal cancer, Ann. Surg., 269, pp. 494-502, (2019)
[4] Manfredi S., Lepage C., Hatem C., Coatmeur O., Faivre J., Bouvier A.M., Epidemiology and management of liver metastases from colorectal cancer, Ann. Surg., 244, pp. 254-259, (2006)
[5] Siegel R.L., Miller K.D., Goding Sauer A., Fedewa S.A., Butterly L.F., Anderson J.C., Cercek A., Smith R.A., Jemal A., Colorectal cancer statistics, 2020, CA Cancer J. Clin., 70, pp. 145-164, (2020)
[6] White M.T., Sears C.L., The microbial landscape of colorectal cancer, Nat. Rev. Microbiol., 22, pp. 240-254, (2024)
[7] Sears C.L., Queen J., Whittling down the bacterial subspecies that might drive colon cancer, Nature, 628, pp. 275-276, (2024)
[8] Sepich-Poore G.D., Zitvogel L., Straussman R., Hasty J., Wargo J.A., Knight R., The microbiome and human cancer, Science, 371, (2021)
[9] Cullin N., Azevedo Antunes C., Straussman R., Stein-Thoeringer C.K., Elinav E., Microbiome and cancer, Cancer Cell, 39, pp. 1317-1341, (2021)
[10] Hanahan D., Hallmarks of cancer: new dimensions, Cancer Discov., 12, pp. 31-46, (2022)

← 1 2 3 4 5 6 →