Role and molecular mechanism of stem cells in colorectal cancer initiation

J Drug Target. 2020 Jan;28(1):1-10. doi: 10.1080/1061186X.2019.1632317. Epub 2019 Jun 27.

Abstract

In recent years, the rate of colorectal cancer has sharply increased, especially in China, where it ranks second for the number of cancer fatalities. Currently, the treatment of colorectal cancer patients involves the combination of resection surgery and treatment with postoperative anticancer drugs such as 5-FU and oxaliplatin. However, recurrence and metastasis after treatment are still the dominant reasons for the low survival rate. Colorectal cancer stem cells (CSCs) are regarded as the key contributors to tumour recurrence and metastasis due to their resistance to chemotherapy drugs and their extremely high tumourigenicity. Once CSCs overcome chemotherapy treatment, they continue to survive and reinitiate proliferation to form tumours, leading to recurrence. The dominant reason for CSC resistance is that most anticancer drugs are aimed at inhibiting proliferative pathways in cancer cells that differ from those in CSCs. Therefore, studies on the characteristics of CSCs and their intracellular molecular pathways are essential for the exploration of CSC-targeted drugs. In this report, we review recent advances in the research of CSCs and, in particular, review the important intracellular molecular pathways, such as HOXA5-catenin, STRAP-NOTCH and YAP/TAZ, related to the maintenance and differentiation of stem cells to generate a theoretical basis for the exploration of CSC-targeted drugs.

Keywords: Colorectal cancer; Wnt pathway; cancer recurrence and metastasis; cancer stem cells; chemotherapy; drug resistance; molecular mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor
  • Colorectal Neoplasms / pathology*
  • DNA Repair / physiology
  • Drug Resistance, Neoplasm / physiology
  • Humans
  • Membrane Proteins / physiology
  • Neoplasm Metastasis / pathology
  • Neoplasm Recurrence, Local
  • Neoplastic Stem Cells / pathology*
  • RNA-Binding Proteins / metabolism
  • Receptors, Notch / metabolism
  • Transcription Factors / metabolism
  • Wnt Signaling Pathway / physiology

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • RNA-Binding Proteins
  • Receptors, Notch
  • STRAP protein, human
  • Transcription Factors