Related Experiment Video

Updated: Jun 14, 2026

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

RasV12 induces Survivin/AuroraB pathway conferring tumor cell apoptosis resistance

Réda Hadj-Slimane1, Perayot Pamonsinlapatham, Jean-Philippe Herbeuval

  • 1Université Paris Descartes, INSERM Unité 648, CNRS UMR 8601, Chimie et Biochimie Pharmacologique et Toxicologique, Faculté de Médecine, 45 rue des Saints-Pères, 75006 Paris, France.

Cellular Signalling
|April 6, 2010
PubMed

Insights

Interferons alpha and gamma induce apoptosis in Ras(wt) colon cancer cells but not Ras(V12) mutated cells. Targeting Survivin and Aurora-B with siRNA restores interferon sensitivity in Ras(V12) colon cancer cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Interferons (IFNs) alpha and gamma are used with chemotherapy for cancers resistant to IFNs alone.
  • Oncogenic Ras mutations, particularly in colon carcinoma, are linked to IFN resistance, but mechanisms remain unclear.

Purpose of the Study:

  • To investigate the mechanism of interferon resistance in colon carcinoma cells with wild-type (wt) Ras versus mutated Ras (V12).
  • To explore the role of Survivin and Aurora-B in mediating resistance and potential therapeutic strategies using siRNA.

Main Methods:

  • Analysis of apoptosis and proliferation in Ras(wt) and Ras(V12) colon carcinoma cells treated with IFNs using flow cytometry and immunoblotting.
  • Investigation of apoptotic pathways in resistant Ras(V12) cells using siRNA to target key proteins like Survivin and Aurora-B.

Main Results:

  • IFNs alpha and gamma synergized to induce apoptosis in Ras(wt) cells via caspase and PARP-1 cleavage, but not in Ras(V12) cells.
  • siRNA targeting Ras(V12) restored IFN sensitivity in Ras(V12) cells.
  • siRNA targeting Survivin enhanced IFN-induced apoptosis in Ras(wt) cells.
  • Ras(V12) mutation maintained high Survivin and phospho-Aurora-B levels, conferring resistance to IFN-induced apoptosis.
  • Combined siRNA targeting Aurora-B and Survivin restored IFN-induced apoptosis in Ras(V12) cells.

Conclusions:

  • Ras(V12) mutation confers IFN resistance in colon cancer cells through an alternative Survivin/Aurora-B survival pathway.
  • Targeting this pathway with siRNA offers potential therapeutic and diagnostic strategies for IFN-resistant cancers.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...