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Silencing of LASS2/TMSG1 enhances invasion and metastasis capacity of prostate cancer cell

Xiaoyan Xu1, Beiying Liu, Pengcheng Zou

  • 1Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, P.R. China; Department of Pathology, School of Basic Medical Sciences, Inner Monglia Medical College, Huhhot, 010059, P.R. China; Department of Pathology, The Affiliated Hospital of Inner Monglia Medical College, Huhhot, 010059, P.R. China.

Journal of Cellular Biochemistry
|January 24, 2014
PubMed

Insights

Silencing the LASS2/TMSG1 gene in prostate cancer cells boosts Vacuolar H(+) ATPase activity, promoting cell invasion and metastasis. This finding highlights LASS2/TMSG1 as a potential therapeutic target for advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Longevity assurance homolog 2 of yeast LAG1 (LASS2), also known as tumor metastasis suppressor gene 1 (TMSG1), has unclear antitumor mechanisms.
  • LASS2/TMSG1 interacts with the C subunit of Vacuolar H(+) ATPase (V-ATPase), suggesting a role in regulating cell invasion and metastasis.

Purpose of the Study:

  • To investigate the effect of LASS2/TMSG1 gene silencing on prostate carcinoma cell invasion and metastasis.
  • To explore the functional interaction between LASS2/TMSG1 and V-ATPase in prostate cancer.

Main Methods:

  • Utilized small hairpin RNA (shRNA) to silence LASS2/TMSG1 in the human prostate carcinoma cell line PC-3M-2B4.
  • Assessed V-ATPase activity, extracellular hydrogen ion concentration, and matrix metalloproteinase (MMP) activation.
  • Evaluated cell proliferation, survival, and invasion in vitro, and tumor growth and lymph node metastasis in vivo.

Main Results:

  • Silencing LASS2/TMSG1 significantly increased V-ATPase activity and extracellular acidity.
  • This led to enhanced activation of secreted MMP-2 and MMP-9, promoting cell proliferation, survival, and invasion.
  • In vivo studies showed accelerated prostate cancer growth and lymph node metastasis upon LASS2/TMSG1 silencing.

Conclusions:

  • Silencing LASS2/TMSG1 enhances prostate cancer invasion and metastasis by increasing V-ATPase activity.
  • LASS2/TMSG1 acts as a suppressor of invasion and metastasis in prostate cancer.
  • LASS2/TMSG1 represents a promising therapeutic target for advanced prostate cancer.
Keywords:
LASS2/TMSG1PC-3M-2B4 CELLSPROSTATE CARCINOMAVACUOLAR H+ ATPaseshRNA

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