Linlang Guo

Zhujiang Hospital

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Lei Sun

Ocean University of China

Yuchun Niu

Zhujiang Hospital

Yichun Tang

Southern Medical University

Xuyang Zhou

University of Chinese Academy of Sciences

Qiongyao Wang

Southern Medical University

Yan Xiong

Icahn School of Medicine at Mount Sinai

Yueyang Hu

Southern Medical University

Yi Chen

Chinese Center For Disease Control and Prevention

Yue Xu

University of Toronto

Yu Wang

Nanjing University

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Southern Medical University

Zhujiang Hospital

Chinese Academy of Sciences

Nanjing University

Tianjin Medical University

Hebei Medical University

Ocean University of China

Shandong University of Traditional Chinese Medicine

University of California, San Diego

Jiangsu University

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Unveiling Mechanisms of Chemotherapy Resistance: Targeting FOXP1 Phase Separation in Small Cell Lung Cancer

Research Square (Research Square) (2024)

Linlang Guo Yichun Tang Yuchun Niu Yueyang Hu Yi Chen

Abstract Our study elucidates the role of FOXP1 in chemoresistance in SCLC. FOXP1 enhances chemoresistance by regulating SP8 expression through its super-enhancer (SP8-SE), with SP8 mediating resistance via the homologous recombination repair (HRR) pathway. We also discovered that FOXP1 forms punctate nuclear structures indicative of liquid-liquid phase separation ¹, crucial for its transcriptional regulation. Targeting the FOXP1-SP8-HR axis with BRD4 and PARP inhibitors showed synergistic effects in reducing tumor growth in vitro and in patient-derived xenograft models. These findings identify FOXP1 as a critical mediator and marker of chemoresistance in SCLC, providing a foundation for developing targeted therapies to overcome this resistance.

10.21203/rs.3.rs-4876919/v1

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