Transforming growth factor-β signaling pathway in colorectal cancer and its tumor microenvironment

HANDLE Open Access
  • Itatani, Yoshiro
    Department of Surgery, Graduate School of Medicine, Kyoto University
  • Kawada, Kenji
    Department of Surgery, Graduate School of Medicine, Kyoto University
  • Sakai, Yoshiharu
    Department of Surgery, Graduate School of Medicine, Kyoto University

Abstract

Transforming growth factor-beta (TGF-β) signaling is one of the important cellular pathways that play key roles for tissue maintenance. In particular, it is important in the context of inflammation and tumorigenesis by modulating cell growth, differentiation, apoptosis, and homeostasis. TGF-β receptor type 2 (TGFBR2) mutations affected by a mismatch repair deficiency causes colorectal cancers (CRCs) with microsatellite instability, which is, however, associated with relatively better survival rates. On the other hand, loss of SMAD4, a transcription factor in the TGF-β superfamily signaling, promotes tumor progression. Loss of heterozygosity on chromosome 18 can case SMAD4-deficient CRC, which results in poorer patients’ survival. Such bidirectional phenomenon driven by TGF-β signaling insufficiency reflects the complexity of this signaling pathway in CRC. Moreover, recent understanding of CRC at the molecular level (consensus molecular subtype classification) provides deep insight into the important roles of TGF-β signaling in the tumor microenvironment. Here we focus on the TGF-β signaling in CRC and its interaction with the tumor microenvironment. We summarize the molecular mechanisms of CRC tumorigenesis and progression caused by disruption of TGF-β signaling by cancer epithelial cells and host stromal cells.

Journal

Keywords

Details 詳細情報について

  • CRID
    1050286428479321216
  • NII Article ID
    120006895434
  • ISSN
    16616596
    14220067
  • HANDLE
    2433/255851
  • Text Lang
    en
  • Article Type
    journal article
  • Data Source
    • IRDB
    • CiNii Articles

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