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PLoS Pathog. 2017 Jul 13;13(7):e1006440. doi: 10.1371/journal.ppat.1006440. eCollection 2017 Jul.

Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development.

Author information

1
Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
2
Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America.
3
Department of Gastrointestinal Medical Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
4
Epidemiology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
5
Department of Internal Medicine, University of Texas Health Science Center, Houston, Texas, United States of America.
6
Department of Microbiology and Microbial Genetics, University of Texas Health Science Center, Houston, Texas, United States of America.
7
Harbin Institute of Technology, Harbin, China.
8
Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas, United States of America.
9
Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
10
Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America.
11
Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, College Station, Texas, United States of America.

Abstract

Streptococcus gallolyticus subsp. gallolyticus (Sg) has long been known to have a strong association with colorectal cancer (CRC). This knowledge has important clinical implications, and yet little is known about the role of Sg in the development of CRC. Here we demonstrate that Sg promotes human colon cancer cell proliferation in a manner that depends on cell context, bacterial growth phase and direct contact between bacteria and colon cancer cells. In addition, we observed increased level of β-catenin, c-Myc and PCNA in colon cancer cells following incubation with Sg. Knockdown or inhibition of β-catenin abolished the effect of Sg. Furthermore, mice administered with Sg had significantly more tumors, higher tumor burden and dysplasia grade, and increased cell proliferation and β-catenin staining in colonic crypts compared to mice receiving control bacteria. Finally, we showed that Sg is present in the majority of CRC patients and is preferentially associated with tumor compared to normal tissues obtained from CRC patients. These results taken together establish for the first time a tumor-promoting role of Sg that involves specific bacterial and host factors and have important clinical implications.

PMID:
28704539
PMCID:
PMC5509344
DOI:
10.1371/journal.ppat.1006440
[Indexed for MEDLINE]
Free PMC Article

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