CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling

Lui Ng, Sunny Kit Man Wong, Zheng Huang, Colin Siu Chi Lam, Ariel Ka Man Chow, Dominic Chi Chung Foo, Oswens Siu Hung Lo, Roberta Wen Chi Pang, Wai Lun Law

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

CD26 has been reported as a marker for colorectal cancer stem cells endowed with tumor-initiating properties and capable of colorectal cancer (CRC) metastasis. In this study, we investigated the functional effect of CD26 on CRC angiogenesis and metastasis, and the potential underlying mechanism. The functional effects of CD26 overexpression or repression were determined by a wound healing experiment, and cell migration and invasion assays in vitro and in mouse models. Differentially expressed genes regulated by CD26 were identified by genome-wide mRNA expression array and validated by quantitative PCR. CD26 functionally regulated CRC cell migration and invasion in vitro and angiogenesis and metastasis in vivo. Genome-wide mRNA expression array and qPCR showed that MMP1 was up-regulated in CD26+ subpopulation, and a subsequent experiment demonstrated the regulatory effect of CD26 on MMP1 in CRC cell lines with CD26 repression or overexpression. Furthermore, overexpression of CAV1 abrogated the CD26-regulated MMP1 induction in CRC cell lines. This study demonstrated the functional roles of CD26 in inducing CRC migration, invasion, angiogenesis and metastasis and identified the potential involvement of MMP1 and CAV1 in such process. CD26 is an attractive therapeutic target for combating tumor progression to improve the prognosis of CRC patients.

Original languageEnglish
Article number1181
JournalInternational Journal of Molecular Sciences
Volume23
Issue number3
DOIs
Publication statusPublished - 1 Feb 2022
Externally publishedYes

Keywords

  • CAV1
  • CD26
  • Colorectal cancer (CRC)
  • MMP1
  • Metastasis

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