Alterations of oncogenes expression in NK cells in patients with cancer

Gulnur K Zakiryanova1, Elena Kustova2, Nataliya T Urazalieva2

  • 1Scientific and Technological Park Al-Farabi Kazakh National University, Almaty, Kazakhstan.

Abstract

Insights

Natural killer (NK) cell c-kit/Stem cell factor (SCF) signaling is crucial for their function. Cancer patients exhibit reduced c-kit and c-myc expression in NK cells, potentially impairing anti-tumor activity.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Signaling

Background:

  • C-kit/Stem cell factor (SCF) signaling is vital for natural killer (NK) cell homeostasis, maturation, proliferation, and cytotoxicity.
  • NK cell-specific c-kit deficiency significantly reduces NK cell numbers, highlighting the critical role of this pathway.
  • Human NK cells express both the c-kit receptor and its ligand, SCF (both membrane-bound and soluble forms).

Purpose of the Study:

  • To investigate the c-kit/SCF autocrine loop in peripheral blood NK cells from cancer patients.
  • To characterize the expression of c-kit, SCF, c-myc, and STAT3 in NK cells of cancer patients.

Main Methods:

  • Utilized Smart Flare and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques.
  • Analyzed the expression of c-kit and both membrane-bound and soluble SCF forms in NK cells.
  • Correlated the expression of c-kit and SCF with c-myc and STAT3 expression.

Main Results:

  • Demonstrated significantly decreased expression of proto-oncogenes c-myc and c-kit in NK cells from all cancer patients studied.
  • Observed a correlation between the expression of membrane-bound SCF in NK cells and the presence of remote metastases.
  • Indicated potential dysregulation of STAT3 expression in conjunction with c-kit/SCF and c-myc.

Conclusions:

  • Abnormal c-kit/SCF, c-myc, and STAT3 signaling and expression in NK cells are implicated in defective cytotoxic activity in cancer.
  • These gene expression defects may represent a cause, rather than a consequence, of tumor progression.
  • Suggests a potential mechanism by which cancer compromises NK cell anti-tumor immunity at the molecular level.

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