Candida albicans synergizes with Fusobacterium nucleatum in colorectal cancer progression via the Flo9-RadD interaction

Jialu Li; Chenyi Zhang; Xinhua Huang; Hongxiang Sun; Lei Yang; Hongzhi Liu; Lu Zhang; Ningbo Wu; Yuanhong Xie; Jingjing Qi; Xiaoxu Leng; Yun Cui; Song Li; Ziran Kang; Zhuolei Kou; Ning-Ning Liu; Pengfei Lan; Beilei Xuan; Dengfeng Cao; Guo-Xiang Cai; Yingxuan Chen; Jianfeng Chen; Zhaoyuan Liu; Florent Ginhoux; Changbin Chen; Bing Su; Jing-Yuan Fang

doi:10.1016/j.ccell.2026.02.001

Candida albicans synergizes with Fusobacterium nucleatum in colorectal cancer progression via the Flo9-RadD interaction

Cancer Cell. 2026 Feb 26:S1535-6108(26)00100-5. doi: 10.1016/j.ccell.2026.02.001. Online ahead of print.

Authors

Jialu Li¹, Chenyi Zhang², Xinhua Huang³, Hongxiang Sun⁴, Lei Yang⁵, Hongzhi Liu⁶, Lu Zhang², Ningbo Wu⁶, Yuanhong Xie², Jingjing Qi⁶, Xiaoxu Leng², Yun Cui², Song Li⁶, Ziran Kang², Zhuolei Kou², Ning-Ning Liu⁷, Pengfei Lan⁸, Beilei Xuan⁹, Dengfeng Cao⁹, Guo-Xiang Cai¹⁰, Yingxuan Chen², Jianfeng Chen¹¹, Zhaoyuan Liu⁶, Florent Ginhoux¹², Changbin Chen¹³, Bing Su¹⁴, Jing-Yuan Fang¹⁵

Affiliations

¹ Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Gastroenterology, Center for Immune-Related Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
² Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
³ Joint Laboratory for Biomedical Research and Pharmaceutical Innovation, The Unit of Pathogenic Fungal Infection & Host Immunity, Shanghai Institute of Materia Medica, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
⁴ Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Gastroenterology, Center for Immune-Related Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁵ Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
⁶ Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁷ State Key Laboratory of Systems Medicine for Cancer, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁸ Institute of Aging & Tissue Regeneration, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
⁹ Dapartment of Pathology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
¹⁰ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
¹¹ Frontier Innovation Center, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, Chinese Academy of Sciences, Hangzhou 310024, China.
¹² Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; INSERM U1015, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Singapore Immunology Network, A(∗)STAR, Singapore 138648, Singapore.
¹³ Joint Laboratory for Biomedical Research and Pharmaceutical Innovation, The Unit of Pathogenic Fungal Infection & Host Immunity, Shanghai Institute of Materia Medica, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: cbchen@ips.ac.cn.
¹⁴ Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Gastroenterology, Center for Immune-Related Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: bingsu@sjtu.edu.cn.
¹⁵ Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China. Electronic address: jingyuanfang@sjtu.edu.cn.

PMID: 41759520
DOI: 10.1016/j.ccell.2026.02.001

Abstract

Fusobacterium nucleatum tumor infiltration is a hallmark of colorectal cancer (CRC) progression. However, whether and how other microbes influence F. nucleatum in CRC remains unclear. Here, we discover that the commensal fungus Candida albicans synergizes with F. nucleatum to promote CRC pathogenesis and contributes to poor patient outcomes. Co-inoculation of C. albicans and F. nucleatum accelerates CRC progression compared to either microbe alone in animal models. C. albicans strains isolated from CRC patients exhibiting enhanced hyphal morphogenesis and elevated FLO9 expression promote F. nucleatum-mediated tumor growth. Mechanistically, through the Flo9-RadD interaction, C. albicans facilitates F. nucleatum localization to the colonic mucosa and promotes F. nucleatum-driven malignant transformation. Translationally, we demonstrate that L-arginine disrupts the interaction between C. albicans and F. nucleatum, reducing their synergistic pro-tumor activity in CRC models in vivo. These findings highlight fungal-bacterial interaction as a critical etiologic mechanism in CRC and a potential therapeutic target.

Keywords: Candida albicans; Flo9; Fusobacterium nucleatum; RadD; colorectal cancer; fungi; microbiota.