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Enhanced radiosensitivity of NSCLC cells by transducer of erbB2.1 (TOB1) through modulation of the MAPK/ERK pathway

Ke-Kang Sun1, Ning Zhong, Yang Yang

  • 1Department of Gastrointestinal Surgery Division of Thoracic Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300, PR China.

Oncology Reports
|April 17, 2013
PubMed

Insights

Transducer of erbB2.1 (TOB1) enhances lung cancer cell radiosensitivity by modulating DNA repair and cell cycle arrest via the MAPK/ERK pathway. This suggests TOB1 is a potential molecular target for improving radiation therapy outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • Transducer of erbB2.1 (TOB1) is an anti-proliferative protein family member.
  • TOB1 overexpression enhances radiosensitivity in breast and cervical cancers.
  • Mechanisms of TOB1 in lung cancer radiosensitivity remain unclear.

Purpose of the Study:

  • To investigate the role of TOB1 in modulating lung cancer cell radiosensitivity.
  • To elucidate the molecular mechanisms underlying TOB1's effect on radiosensitivity.

Main Methods:

  • Evaluated IR-induced TOB1 expression in NCI-H1975 and A549 lung cancer cells using Western blot.
  • Established TOB1 gain-of-function (plasmid transfection) and loss-of-function (siRNA) models.
  • Assessed clonogenic survival, cell cycle distribution, DNA repair (γ-H2AX foci), and MAPK/ERK pathway activation.

Main Results:

  • IR significantly induced TOB1 expression.
  • TOB1 overexpression reduced clonogenic survival and abrogated G2/M arrest but enhanced γ-H2AX foci post-irradiation.
  • TOB1 silencing showed opposite effects.
  • TOB1 modulated MAPK activation and p53 phosphorylation via the MAPK/ERK pathway.

Conclusions:

  • TOB1 expression is induced by IR in lung cancer cells.
  • TOB1 plays a crucial role in regulating lung cancer cell radiosensitivity.
  • The MAPK/ERK signaling pathway is involved in TOB1-mediated radiosensitization.

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