Key Takeaways & Executive Findings
- •• E. faecalis down-regulates MOB3B expression in colorectal cancer cells, promoting chemoresistance. • MOB3B overexpression reduces cell viability and reverses chemoresistance to oxaliplatin and 5-fluorouracil. • MOB3B modulates chemoresistance in an LRRC19-dependent manner, linking the Hippo pathway to drug resistance. • Low MOB3B expression correlates with high Tumour Regression Grade, indicating its potential as a prognostic and chemosensitivity marker.
Abstract
AIM: To investigate the contribution of Enterococcus faecalis (E. faecalis) to chemoresistance in colorectal cancer (CRC) and uncover the underlying mechanisms. METHODS: Bioinformatics analyses were performed to evaluate the expression of MOB3B, an Mps-one binder coactivator (MOB) protein family member, and its clinical implications in CRC patients. E. faecalis was co-cultured with CRC cells to assess its effect on MOB3B expression. MOB3B was overexpressed or silenced in CRC cells to determine its effects on cell viability and chemosensitivity. The LRRC19-dependent mechanism was investigated through additional bioinformatics analyses. Immunohistochemical staining of clinical CRC tissues was performed to correlate MOB3B expression with Tumour Regression Grade. RESULTS: MOB3B down-regulation was associated with adverse clinicopathological characteristics and poor prognosis in CRC patients. Co-culture with E. faecalis down-regulated MOB3B expression in CRC cells. MOB3B overexpression decreased cell viability, while its silencing increased viability. MOB3B overexpression also reversed chemoresistance in CRC cells. Bioinformatics analyses revealed that MOB3B modulated resistance to oxaliplatin and 5-fluorouracil in an LRRC19-dependent manner. Low MOB3B expression correlated with high Tumour Regression Grade in clinical tissues. CONCLUSION: These findings indicate that Enterococcus faecalis promotes chemotherapy resistance by down-regulating MOB3B in colorectal cancer, and that MOB3B may serve as a potential marker for evaluating chemosensitivity and prognosis in CRC patients. The role of E. faecalis abundance as a clinical biomarker requires further validation in prospective cohorts.
1. Introduction
Enterococci are ubiquitous in nature and normally found in the upper respiratory tract, intestinal tract, and oral cavity of healthy humans. Enterococcus faecalis (E. faecalis), a facultatively anaerobic, gram-positive coccobacillus, is one of the dominant bacterial species in the human gut and demonstrates strong resilience and colonisation ability in the intestinal mucosa. Certain E. faecalis strains exhibit probiotic properties, including the production of bacteriocins and other antibacterial substances that improve the intestinal microenvironment and inhibit pathogenic bacteria such as E. coli and Salmonella. Although its beneficial effects have been demonstrated in several strains and its long-term safe use has been documented, E. faecalis remains an opportunistic pathogen capable of causing hospital-acquired infections, raising safety concerns. Recently, E. faecalis has been detected in pancreatic cancer, breast cancer, and liver cancer tissues.
Colorectal cancer (CRC) is the third most common malignant cancer and the second leading cause of cancer-related death worldwide. Chemotherapy remains the first-line treatment for advanced CRC, aiming to reduce tumour size, slow growth, and inhibit metastasis. Combination therapy with 5-fluorouracil (5-FU) and oxaliplatin is widely used in clinical practice. Although most patients with advanced CRC initially respond well to combination therapy, drug resistance commonly develops, leading to tumour recurrence and a 5-year survival rate of less than 10%. Moreover, only a small proportion of patients benefit from novel immune checkpoint therapies. Therefore, elucidating the mechanisms underlying chemoresistance in CRC is of critical importance.
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ZHANG Weiyang, QI Jingru, ZHAO Zhuoyang, YANG Longan, YAN Yongrong, LI Yuxuan, SHUAI Xinran, WU Gongfa, SONG Jiawei, HUA Xing, ZHOU Rui, YU Lina (2026). Enterococcus faecalis Promotes Chemotherapy Resistance by Down-regulating MOB3B in Colorectal Cancer. Chinese Journal of Pathophysiology. https://doi.org/10.3969/j.issn.1000-4718.2026.06.009
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Frequently Asked Questions
What is the role of Enterococcus faecalis in colorectal cancer chemoresistance?
The study demonstrates that E. faecalis promotes chemotherapy resistance in colorectal cancer by down-regulating MOB3B expression, which in turn activates pro-survival pathways and drug-efflux pumps, leading to reduced sensitivity to oxaliplatin and 5-fluorouracil.
How does MOB3B affect chemotherapy sensitivity in colorectal cancer?
MOB3B overexpression decreases cell viability and reverses chemoresistance in CRC cells, while its silencing increases viability. MOB3B modulates resistance to oxaliplatin and 5-fluorouracil in an LRRC19-dependent manner, suggesting it as a potential marker for chemosensitivity.
What is the clinical significance of MOB3B expression in colorectal cancer patients?
Low MOB3B expression is associated with adverse clinicopathological characteristics, poor prognosis, and high Tumour Regression Grade, indicating that MOB3B may serve as a prognostic marker and a predictor of chemotherapy response in CRC patients.
What is the underlying mechanism by which E. faecalis down-regulates MOB3B?
The study suggests that E. faecalis co-culture down-regulates MOB3B expression in CRC cells, but the exact molecular mechanism is not fully elucidated. It is hypothesized that E. faecalis may modulate host signaling pathways, possibly through inflammatory or metabolic mediators, leading to MOB3B suppression.
Can E. faecalis abundance be used as a clinical biomarker for chemoresistance?
The study suggests that E. faecalis abundance may have potential as a clinical biomarker, but further validation in prospective cohorts is required before it can be used in clinical practice.
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