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Upstream transcription factor 1 suppresses laryngeal squamous cell carcinoma progression through transcriptional

Yue Jia1,2,3, Jiaojiao Liu1,2,3, Yichen Lou1,2,3

  • 1Department of First Clinical Medicine, Shanxi Medical University, Taiyuan, China.

IUBMB Life
|March 12, 2025
PubMed

Insights

Upstream stimulatory factor 1 (USF1) enhances junctional adhesion molecule 3 (JAM3) expression, suppressing laryngeal squamous cell carcinoma (LSCC) growth. This USF1-JAM3 axis activates the Hippo pathway, offering new therapeutic targets for LSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Laryngeal squamous cell carcinoma (LSCC) is aggressive and treatment-resistant.
  • Junctional adhesion molecule 3 (JAM3) is a known tumor suppressor in LSCC.
  • The upstream regulators of JAM3 in LSCC remain largely uncharacterized.

Purpose of the Study:

  • To investigate the transcriptional regulation of JAM3 by upstream stimulatory factor 1 (USF1) in LSCC.
  • To elucidate the role of the USF1-JAM3 axis in LSCC pathogenesis and tumor suppression.
  • To explore the therapeutic potential of targeting USF1 and JAM3 in LSCC.

Main Methods:

  • Dual-luciferase assays and ChIP-qPCR to confirm USF1 binding to the JAM3 promoter.
  • In vitro and in vivo experiments to assess the impact of USF1 overexpression on LSCC aggressiveness.
  • Western blot and immunohistochemistry to analyze Hippo signaling pathway activation.

Main Results:

  • USF1 directly binds to the JAM3 promoter, enhancing JAM3 expression in LSCC cells.
  • USF1 overexpression significantly reduces LSCC tumor aggressiveness, correlating with increased JAM3 activity.
  • USF1-induced JAM3 activation triggers the Hippo signaling pathway, contributing to tumor suppression.

Conclusions:

  • USF1 acts as a transcriptional activator of JAM3 in LSCC.
  • The USF1-JAM3 interaction suppresses LSCC progression via the Hippo signaling pathway.
  • USF1 and JAM3 represent promising therapeutic targets for laryngeal squamous cell carcinoma.
Keywords:
hippo signaling pathwayjunctional adhesion molecule 3 (JAM3)laryngeal squamous cell carcinoma (LSCC)transcription factorupstream stimulatory factor 1 (USF1)

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