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Farnesoid X receptor promotes non-small cell lung cancer metastasis by activating Jak2/STAT3 signaling via transactivation of IL-6ST and IL-6 genes

  • 0Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
Cell Death & Disease +

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February 15, 2024

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February 15, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Farnesoid X Receptor (FXR) promotes non-small cell lung cancer (NSCLC) metastasis by activating the IL-6/IL-6ST/Jak2/STAT3 pathway. Inhibiting FXR may offer a new treatment for metastatic NSCLC.

Area Of Science

  • Oncology
  • Molecular Biology
  • Biochemistry

Background

  • Metastasis is a primary cause of mortality in advanced non-small cell lung cancer (NSCLC).
  • Farnesoid X Receptor (FXR), a bile acid nuclear receptor, is upregulated in NSCLC, but its role in metastasis is unknown.

Purpose Of The Study

  • To investigate the role of FXR in NSCLC metastasis.
  • To elucidate the underlying molecular mechanisms of FXR-mediated metastasis.
  • To evaluate FXR as a potential therapeutic target for metastatic NSCLC.

Main Methods

  • In vitro assays (migration, invasion, angiogenesis) using NSCLC cells.
  • In vivo mouse models of NSCLC metastasis.
  • Mechanistic studies involving gene promoter binding and signaling pathway analysis (IL-6, IL-6ST, Jak2/STAT3).
  • Pharmacological inhibition of FXR using Z-guggulsterone.
  • Clinical correlation analysis in NSCLC patient samples.

Main Results

  • FXR significantly promoted NSCLC cell migration, invasion, and angiogenesis in vitro.
  • FXR enhanced NSCLC metastasis in vivo.
  • FXR upregulates IL-6 and IL-6ST expression, activating the Jak2/STAT3 pathway, which drives tumor progression.
  • Z-guggulsterone treatment reduced metastasis and key molecular markers in mice.
  • Clinical data showed a positive correlation between FXR, IL-6, IL-6ST, p-STAT3, and poor prognosis in NSCLC patients.

Conclusions

  • A novel FXR-induced IL-6/IL-6ST/Jak2/STAT3 signaling axis promotes NSCLC metastasis.
  • FXR is a potential therapeutic target for treating FXR-high metastatic NSCLC.
  • FXR status can serve as a prognostic biomarker in NSCLC.

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