KRT14 Drives Basal Muscle‐Invasive Bladder Cancer Progression and Lung Metastasis by Directly Binding to and Stabilizing IGF2BP1
Source abstract
Abstract
ABSTRACT Basal‐type muscle‐invasive bladder cancer (BMIBC) is characterized by aggressive metastasis and poor prognosis but lacks molecularly defined therapeutic targets. Through integrative analyses of clinical cohorts and BBN‐induced mouse models, we identified KRT14 as a core oncogenic driver that orchestrates the KRT14‐IGF2BP1 signaling axis to promote BMIBC progression and lung metastasis. Mechanistically, residues K294 and E295 within the KH2 domain of IGF2BP1 specifically recognize conserved residues D226 and E227 within the nuclear export signal of KRT14. This direct interaction facilitates IGF2BP1‐mediated cytoplasmic trafficking and auto‐stabilization of its own mRNA, establishing a positive feedback loop that amplifies IGF2BP1‐targeted pro‐invasive gene expression. Functional disruption of this axis suppressed primary tumor progression and lung metastasis in BMIBC models. Collectively, our findings define the KRT14‐IGF2BP1 axis as a previously unrecognized, potentially targetable vulnerability in BMIBC, whose inhibition may limit aggressive disease progression and inform future therapeutic strategies.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Bladder and Urothelial Cancer Treatments · Ferroptosis and cancer prognosis · Hedgehog Signaling Pathway Studies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Key Laboratory of Medicine Ministry of Education School of Laboratory Medicine and Life Sciences Wenzhou Medical University Wenzhou Zhejiang China
Oujiang Laboratory Zhejiang Lab for Regenerative Medicine, Vision and Brain Health Wenzhou Zhejiang China
The Department of General Surgery the Second Hospital of Hebei Medical University Shijiazhuang Hebei China
The Second Department of Surgery the Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China
Center of Biomedical Physics Wenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang China
Department of Occupational Health and Environmental Health School of Public Health Anhui Medical University Hefei Anhui China
Department of Oncology The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
Department of General Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
Department of Urology The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
Funding
National Natural Science Foundation of China
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