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Effects of RhoA and RhoC upon the sensitivity of prostate cancer cells to glutamine deprivation

Luciana Bueno De Paiva1, Vanessa Aline Bernusso1, João Agostinho Machado-Neto2,3

  • 1Hematology and Bloood Transfusion Center, University of Campinas , Campinas, São Paulo, Brazil.

Small Gtpases
|November 20, 2018
PubMed

Insights

RhoA and RhoC proteins regulate glutamine metabolism, impacting cancer cell growth. Inhibiting these proteins, RhoA (Ras homolog family member A) and RhoC, may enhance prostate cancer treatments targeting glutamine pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Metabolism

Background:

  • Glutamine metabolism is critical for cancer cell proliferation and survival.
  • RhoA and RhoC are small GTPases involved in cell signaling and cytoskeletal regulation.
  • The role of RhoA and RhoC in prostate cancer cell response to glutamine deprivation remains unclear.

Purpose of the Study:

  • To investigate the involvement of RhoA and RhoC in prostate cancer cell adaptation to glutamine deprivation.
  • To determine the impact of RhoA and RhoC activity modulation on prostate cancer cell viability under glutamine-limited conditions.

Main Methods:

  • Utilized PC3 and LNCaP prostate cancer cell lines.
  • Assessed RhoA and RhoC activities in response to glutamine reduction.
  • Examined the effect of stable overexpression of wild-type RhoA/RhoC and dominant-negative mutants (RhoAN19, RhoCN19) on cell proliferation and survival under glutamine deprivation.

Main Results:

  • Glutamine reduction led to altered RhoA and RhoC activities in PC3 and LNCaP cells, correlating with reduced cell number and proliferation.
  • Stable overexpression of wild-type RhoA or RhoC did not affect sensitivity to glutamine deprivation.
  • PC3 cells expressing dominant-negative RhoAN19 or RhoCN19 mutants exhibited increased resistance to glutamine deprivation.

Conclusions:

  • RhoA and RhoC activities play a significant role in prostate cancer cell response to glutamine deprivation.
  • Modulating RhoA and RhoC activity could represent a therapeutic strategy to enhance the efficacy of cancer treatments targeting glutamine metabolism.
Keywords:
LNCaP cellsPC3 cellsRho GTPasesRhoARhoCglutamineprostate cancer

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