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Silencing the Snail-Dependent RNA Splice Regulator ESRP1 Drives Malignant Transformation of Human Pulmonary

Tonya C Walser1,2,3, Zhe Jing1,2,3, Linh M Tran1,2,3

  • 1Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.

Cancer Research
|February 13, 2018
PubMed

Insights

The epithelial-to-mesenchymal transition (EMT) transcription factor Snail promotes lung cancer by silencing ESRP1. This Snail-ESRP1 axis is critical in lung carcinogenesis and offers new therapeutic targets for non-small cell lung cancer (NSCLC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Epithelial-to-mesenchymal transition (EMT) is implicated in cancer progression, but its role in non-small cell lung cancer (NSCLC) requires further elucidation.
  • Key transcription factors orchestrate EMT, yet their specific contributions and downstream effects in lung carcinogenesis are not fully understood.

Purpose of the Study:

  • To investigate the role of the EMT-inducing transcription factor Snail in lung carcinogenesis.
  • To determine the relationship between Snail, ESRP1, and stem cell populations in NSCLC development.
  • To identify potential therapeutic targets for NSCLC based on the Snail-ESRP1 axis.

Main Methods:

  • Analysis of Snail expression in premalignant pulmonary lesions and NSCLC specimens.
  • In vitro and in vivo studies using immortalized human pulmonary epithelial cells to assess Snail's functional impact.
  • Investigation of Snail-mediated silencing of ESRP1 and its effect on stem cell markers (ALDH+, CD44+, CD24-) and microRNAs.

Main Results:

  • Snail expression is increased in premalignant lesions compared to normal lung tissue.
  • Snail promotes anchorage-independent growth in vitro and enhances tumor growth and metastasis in vivo.
  • Snail-induced transformation involves the silencing of tumor suppressor ESRP1, particularly in an ALDH+CD44+CD24- stem cell subset.

Conclusions:

  • ESRP1 loss, driven by Snail, is a critical event in human lung carcinogenesis.
  • The Snail-ESRP1 axis plays a crucial role in driving malignant progression in NSCLC.
  • Targeting the Snail-ESRP1 pathway presents a promising strategy for novel NSCLC therapies.

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