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Sestrin 2 suppresses cells proliferation through AMPK/mTORC1 pathway activation in colorectal cancer

Jin-Lai Wei1, Min Fang2, Zhong-Xue Fu1

  • 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Oncotarget
|May 20, 2017
PubMed

Insights

Sestrin 2, an antioxidant protein, suppresses colorectal cancer (CRC) growth by reducing reactive oxygen species (ROS) and activating the AMPK/mTORC1 pathway. Overexpression of sestrin 2 inhibits CRC cell proliferation and promotes apoptosis, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Sestrin 2 is an antioxidant protein known to reduce reactive oxygen species (ROS) and inhibit mammalian target of rapamycin complex 1 (mTORC1).
  • Previous studies indicated that sestrin 2 levels are abnormally decreased in colorectal cancer (CRC).

Purpose of the Study:

  • To investigate the molecular mechanisms by which sestrin 2 influences colorectal cancer progression.
  • To determine the effects of sestrin 2 overexpression on human CRC cell lines and a xenograft mouse model.

Main Methods:

  • Utilized a lentiviral expression vector system for sestrin 2 overexpression in human CRC cells.
  • Assessed changes in ROS production, cell proliferation (PCNA), apoptosis (caspases, survivin), and signaling pathways (AMPK, mTORC1).
  • Employed compound C (AMPK inhibitor) and a xenograft mouse model to validate findings.

Main Results:

  • Sestrin 2 overexpression decreased ROS production, inhibited CRC cell growth, and stimulated apoptosis.
  • Increased levels of proapoptotic proteins (caspase 3, 7, 9) and decreased levels of anti-apoptotic protein survivin were observed.
  • Sestrin 2 activated the AMPK pathway, suppressed mTORC1 signaling, and attenuated CRC growth in vivo.

Conclusions:

  • Sestrin 2 suppresses colorectal cancer growth via AMPK/mTORC1 pathway activation and apoptosis induction.
  • Sestrin 2 represents a potential novel pharmacological target for CRC treatment.
Keywords:
AMPKcolorectal cancermTORC1proliferationsestrin 2

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