Targeting the LHX1-LDB1 Complex Restores STING-dependent Senescence Surveillance and Inhibits Head and Neck Cancer Progression

International Journal of Biological Sciences 2026 Open access

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Authors: M.D Long, Yang Chen, Ruixue Du, Jiejie Yang, Jingjing Wang, Yunqing Sun, Xuezhang Tian, Shaowei Wang, Yunhong Zhong, Weilian Liang, Junjie Zhang, Zhengjun Shang
DOI: 10.7150/ijbs.123790
Cited by: 1

Abstract

restored STING-dependent SASP and impaired cancer stem cell self-renewal. Therapeutic disruption of the LHX1-LDB1 complex using engineered peptides re-activated STING signaling, induced SASP, and significantly suppressed tumor growth. In this study, we employed human and mouse-derived HNSCC cell lines, xenograft models, and clinical samples to assess the functional relevance of LHX1 in regulating SASP and tumor progression. Our findings reveal LHX1 as a master transcriptional repressor of STING-mediated senescence and highlight the therapeutic potential of targeting the LHX1-LDB1 axis to restore tumor-suppressive SASP in HNSCC.

Fields of Study & Subjects

interferon and immune responses Protein Degradation and Inhibitors Chromatin Remodeling and Cancer

Publication details

Journal / source
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Volume
22
Issue
3
Pages
1186–1206
Publication date
1 January 2026
Language
EN