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A Sensitive Method to Quantify Senescent Cancer Cells
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Targeting of the C-Jun/BCL-XL/P21 Axis Accelerates the Switch from Senescence to Apoptosis Upon ROC1 Knockdown in

Ping Chen1,2, Xiaoting Luo1, Zhihui Che1

  • 1Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai, China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|July 25, 2018
PubMed
Abstract

Insights

Regulator of cullins-1 (ROC1) high expression correlates with poor gastric cancer prognosis. Targeting BCL-XL enhances ROC1 knockdown

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Regulator of cullins-1 (ROC1) is a key component of E3 ubiquitin ligases involved in substrate degradation.
  • The role of ROC1 in gastric cancer pathogenesis remains largely uncharacterized.
  • Investigating ROC1's function and prognostic significance in gastric cancer is crucial.

Purpose of the Study:

  • To determine the relationship between ROC1 expression and gastric cancer patient prognosis.
  • To explore the biological functions of ROC1 in gastric cancer.
  • To elucidate the underlying molecular mechanisms of ROC1 in gastric cancer progression.

Main Methods:

  • Kaplan-Meier and multivariate Cox regression analyses for ROC1 correlation with gastric cancer.
  • SA-β-gal staining and SASP assessment for ROC1 silencing-induced cellular senescence.
  • Xenograft zebrafish models to evaluate co-silencing effects of BCL-XL and ROC1 on tumor formation.

Main Results:

  • High ROC1 expression is linked to poor prognosis and reduced 5-year survival in gastric cancer patients.
  • ROC1 depletion inhibits gastric cancer cell growth via p21-mediated senescence and apoptosis.
  • The c-Jun/BCL-XL/p21 axis promotes senescence, resisting apoptosis upon ROC1 knockdown.

Conclusions:

  • The c-Jun/BCL-XL/p21 pathway mediates senescence as a resistance mechanism to ROC1 knockdown-induced apoptosis in gastric cancer.
  • Targeting BCL-XL can sensitize gastric cancer cells to ROC1 knockdown, offering potential clinical strategies.
Keywords:
ApoptosisBCL-XLC-JunGastric cancerP21ROC1Senescence

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