Yes is a central mediator of cell growth in malignant mesothelioma cells

Our plain-English summary of Yes is a central mediator of cell growth in malignant mesothelioma cells, by A. Sato, M. Sekine, N. Virgona, et al (Oncology Reports, 2012).

The study

• Authors: A. Sato, M. Sekine, N. Virgona, M. Ota, T. Yano
• Journal: Oncology Reports
• Published: 2012;28(5):1889-93
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The constitutive activation of the Src family kinases (SFKs) has been established as a poor prognostic factor in malignant mesothelioma (MM), however, the family member(s) which contribute to the malignancy have not been defined. This study aimed to identify the SFK member(s) contributing to cell growth using RNA interference in various MM cell lines. Silencing of Yes but not of c-Src or Fyn in MM cells leads to cell growth suppression. This suppressive effect caused by Yes silencing mainly depends on G1 cell cycle arrest and partly the induction of apoptosis. Also, the knockout of Yes induces the inactivation of β-catenin signaling and subsequently decreases the levels of cyclin D necessary for G1-S transition in the cell cycle. In addition, Yes knockout has less effect on cell growth suppression in β-catenin-deficient H28 MM cells compared to other MM cells which express the catenin. Overall, we conclude that Yes is a central mediator for MM cell growth that is not shared with other SFKs such as c-Src.

In plain English

This was a laboratory study of human cells grown in dishes. It involved no patients and studied no asbestos exposure. The authors used malignant mesothelioma cell lines (H28, H2052, H2452 and MSTO-211H) and a non-malignant transformed mesothelial cell line (Met5A). They examined three related enzymes from the Src family of kinases, called c-Src, Yes and Fyn, and used siRNA to switch each one down for 48 hours. All three were expressed at significantly higher levels in three mesothelioma lines than in Met5A cells, and Yes had the highest level. Only switching down Yes significantly reduced growth, by 42% in H2452 cells. The authors reported the same effect in two other lines but did not show those data. Switching down Yes stopped cells at an early stage of division (G1 arrest), raised a measure of cell death by about 45%, and lowered cyclin D, a target of beta-catenin signaling. It had less effect in H28 cells, which lack beta-catenin. The authors concluded that Yes is a central mediator of mesothelioma cell growth.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiment on human cell lines, using siRNA (RNA interference) to switch down individual Src family kinases
• Who was studied: Human cell lines from ATCC: one non-malignant transformed mesothelial line (Met5A) and four malignant mesothelioma lines (H28, H2052, H2452 and MSTO-211H). No patients or tissue donors were studied.
• Exposure: No asbestos or fiber exposure was studied. The experimental treatment was 48-hour siRNA knockdown of c-Src, Yes or Fyn, compared with a non-specific siRNA control.
• Main results:
  • c-Src, Yes and Fyn were expressed at significantly higher levels in three mesothelioma cell lines (H2052, H2452, MSTO-211H) than in non-tumorigenic Met5A cells. Of the three, Yes had the highest level.
  • In H2452 cells, only knockdown of Yes significantly reduced cell growth, by 42%. The authors reported the same effect in H2052 and MSTO-211H cells but did not show those data.
  • In H2452 cells, Yes knockdown induced G1 cell cycle arrest and significantly increased the subG1 population, which the authors used as a sign of apoptosis, by about 45%.
  • In H2452 cells, Yes knockdown moved beta-catenin back to the cell membrane fraction and reduced cyclin D.
  • Yes knockdown had less effect on growth in beta-catenin-deficient H28 cells than in H2452 cells, which express beta-catenin.
• The authors' conclusion: The authors concluded that, among the Src family kinases examined, only silencing Yes was associated with suppressed growth of mesothelioma cells. In their view, this indicates that Yes is a central mediator of mesothelioma cell growth.
• Limitations the authors state:
  • The authors stated that why Yes has a specific effect on mesothelioma cell growth is still unclear.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Apoptosis.

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• Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells — Y.J. Lee, I.S. Hwang, et al. (2014)
• A Succinate Ether Derivative of Tocotrienol Enhances Dickkopf-1 Gene Expression through Epigenetic Alterations in Malignant Mesothelioma Cells — A. Sato, H. Ueno, et al. (2018)
• PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells — A.S. Mawas, V.J. Amatya, et al. (2017)
• Inhibition of REV3 expression induces persistent DNA damage and growth arrest in cancer cells — P.A. Knobel, I.N. Kotov, et al. (2011)

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