The DEAD box protein p68: a novel coactivator of Stat3 in mediating oncogenesis

M Sarkar1, V Khare1, M K Ghosh1

  • 1Signal Transduction in Cancer and Stem Cells Laboratory, Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata, India.

Oncogene
|December 13, 2016
PubMed

Insights

The DEAD box RNA helicase p68 protein directly interacts with Signal transducer and activator of transcription 3 (Stat3), enhancing Stat3

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • DEAD box RNA helicase p68 is a transcriptional coactivator involved in RNA metabolism.
  • Signal transducer and activator of transcription 3 (Stat3) is a key oncogenic factor in various cancers, including colon cancer.

Purpose of the Study:

  • To elucidate the novel mechanism of p68 and Stat3 interaction in transcriptional coactivation.
  • To investigate the role of p68 in Stat3-mediated oncogenesis in colon cancer.

Main Methods:

  • Co-immunoprecipitation assays to demonstrate direct interaction between p68 and Stat3.
  • Quantitative PCR and Western blotting to assess target gene expression.
  • Reporter assays to measure promoter activity.
  • In vivo mouse models (colorectal allograft) to evaluate oncogenic effects.

Main Results:

  • p68 and Stat3 expression show a positive correlation and colocalization in colon cancer samples.
  • p68 directly interacts with Stat3 in cancer cells and enhances Stat3 target gene expression and promoter activity.
  • p68 enhances Stat3-dependent transcription by occupying target gene promoters.
  • p68-expressing cells lead to increased Stat3 target gene expression in tumors and metastases in vivo.

Conclusions:

  • This study reveals a novel mechanism where p68 coactivates Stat3, promoting Stat3-mediated oncogenesis.
  • p68 enhances Stat3 signaling, contributing to colon cancer progression.
  • Targeting the p68-Stat3 interaction could offer new therapeutic strategies for colon cancer.

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