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Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
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Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines

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Stathmin1 increases radioresistance by enhancing autophagy in non-small-cell lung cancer cells

Xi Zhang1, Jingfen Ji2, Yu Yang3

  • 1Department of Oncology, Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China; Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.

Oncotargets and Therapy
|May 21, 2016
PubMed

Insights

Stathmin1 (STMN1) promotes radioresistance in non-small-cell lung cancer (NSCLC) by inducing autophagy via the PI3K/mTOR pathway. Targeting STMN1 may improve NSCLC radiotherapy outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • Radioresistance contributes to poor prognosis in non-small-cell lung cancer (NSCLC).
  • The molecular mechanisms underlying NSCLC radioresistance are not fully understood.
  • Identifying therapeutic targets is crucial for enhancing radiotherapy efficacy in NSCLC.

Purpose of the Study:

  • To investigate the role of Stathmin1 (STMN1) in NSCLC radioresistance.
  • To elucidate the underlying molecular mechanisms, including autophagy and signaling pathways.
  • To explore the relationship between STMN1, miR-101, and autophagy in NSCLC.

Main Methods:

  • Analysis of STMN1 protein levels in irradiated NSCLC cells.
  • Assessment of autophagy activation and its modulation by STMN1.
  • Investigation of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway.
  • Luciferase reporter assays to confirm STMN1 as a miR-101 target gene.

Main Results:

  • STMN1 protein levels and autophagy were upregulated in NSCLC cells upon radiation exposure.
  • STMN1 knockdown increased NSCLC cell sensitivity to X-ray and inhibited radiation-induced autophagy.
  • STMN1 knockdown upregulated PI3K/mTOR signaling, which inhibited autophagy and radioresistance.
  • STMN1 was identified as a direct target gene of miR-101.

Conclusions:

  • STMN1 promotes NSCLC radioresistance by inducing autophagy through the PI3K/mTOR signaling pathway.
  • STMN1 acts as a downstream effector of miR-101 in regulating autophagy and radioresistance.
  • STMN1 represents a potential therapeutic target to overcome radioresistance in NSCLC radiotherapy.
Keywords:
PI3KSTMN1autophagymTOR pathwaynon-small-cell lung cancerradioresistance

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