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NFATC2 is a novel therapeutic target for colorectal cancer stem cells

Tingyuan Lang1, Xiaojuan Ding1, Liangsheng Kong1

  • 1Key Laboratory of Laboratory Medical Diagnostics (Ministry of Education of China), Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People's Republic of China, dingshijia@163.com, hxju@nju.edu.cn.

Oncotargets and Therapy
|November 10, 2018
PubMed
Abstract

Insights

Nuclear Factor of Activated T-cells 2 (NFATC2) promotes colorectal cancer stem cell (CRC-SC) propagation. Targeting NFATC2 may offer a new therapeutic strategy for colorectal cancer (CRC).

Area of Science:

  • Oncology
  • Cancer Stem Cell Biology
  • Molecular Mechanisms of Cancer

Background:

  • Colorectal cancer stem cells (CRC-SCs) are crucial for colorectal cancer (CRC) initiation and progression.
  • The mechanisms driving CRC-SC propagation remain largely unknown.
  • Understanding these mechanisms is vital for developing effective CRC therapies.

Purpose of the Study:

  • To investigate the role of NFATC2 in maintaining stemness in CRC-SCs.
  • To elucidate the molecular pathways through which NFATC2 influences CRC-SC properties.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and Western blot for gene and protein expression analysis.
  • Spheroid formation assay and flow cytometry for CRC-SC isolation and characterization.
  • Cell-derived xenograft models to assess tumorigenicity.
  • Lentivirus-mediated gene delivery for NFATC2 manipulation.

Main Results:

  • NFATC2 expression is upregulated in primary CRC-SCs.
  • Overexpression of NFATC2 enhances self-renewal and stem cell marker expression in CRC-SCs.
  • Knockdown of NFATC2 diminishes stem cell-like properties.
  • NFATC2 upregulates AJUBA, reduces YAP phosphorylation, and activates YAP transcriptional activity, promoting CRC-SC stemness.

Conclusions:

  • NFATC2 functions as an oncogene promoting CRC-SC stemness.
  • Aberrant NFATC2 expression presents a potential therapeutic target for CRC.
  • This study highlights a novel therapeutic strategy for CRC targeting NFATC2.
Keywords:
NFATC2YAPcolorectal cancerstem cellsstemness

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