TY - JOUR
T1 - Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development
AU - Kumar, Ritesh
AU - Herold, Jennifer L.
AU - Schady, Deborah
AU - Davis, Jennifer
AU - Kopetz, Scott
AU - Martinez-Moczygemba, Margarita
AU - Murray, Barbara E.
AU - Han, Fang
AU - Li, Yu
AU - Callaway, Evelyn
AU - Chapkin, Robert S.
AU - Dashwood, Wan Mohaiza
AU - Dashwood, Roderick H.
AU - Berry, Tia
AU - Mackenzie, Chris
AU - Xu, Yi
N1 - Publisher Copyright:
© 2017 Kumar et al.
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.ppat.1006440
DO - 10.1371/journal.ppat.1006440
M3 - Article
C2 - 28704539
AN - SCOPUS:85026884966
SN - 1553-7366
VL - 13
JO - PLoS pathogens
JF - PLoS pathogens
IS - 7
M1 - e1006440
ER -