ADAM9 Mediates Triple-Negative Breast Cancer Progression via AKT/NF-κB Pathway

Rui Zhou, William C.S. Cho, Victor Ma, Wah Cheuk, Yik Ka So, S. C.Cesar Wong, Mingrong Zhang, Cong Li, Yujie Sun, Hong Zhang, Lawrence W.C. Chan, Mei Tian

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

Upregulation of a disintegrin and metalloprotease 9 (ADAM9) is correlated with progression of cancers, such as prostate, bladder, and pancreatic cancers. However, its role in triple-negative breast cancer (TNBC) is still unclear. Our study aimed to investigate whether ADAM9 is upregulated and promoted the aggressiveness in TNBC. Breast cancer cell lines and patient specimens were used to evaluate the ADAM9 expression by western blotting and immunohistochemistry staining, respectively. Compared with the non-TNBC, ADAM9 expression was significantly increased in TNBC cells and TNBC patient specimens. Based on the data acquired from public databases, the correlation between ADAM9 expression and breast cancer patient survival was analyzed by Kaplan-Meier method. It was shown that ADAM9 overexpression was significantly correlated with poorer survival in patients with TNBC. Furthermore, ADAM9 in TNBC cells was knocked down by small interference RNA and then studied by the MTT/colony formation assay, wound healing assay and transwell invasion assay on the cell proliferation, migration, and invasion, respectively. We found that inhibiting ADAM9 expression suppressed TNBC cell proliferation, migration, and invasion by lowering the activation of AKT/NF-κB pathway. Our results demonstrated that ADAM9 is an important molecule in mediating TNBC aggressiveness and may be a potential useful therapeutic target in TNBC treatment.

Original languageEnglish
Article number214
JournalFrontiers in Medicine
Volume7
DOIs
Publication statusPublished - 19 Jun 2020

Keywords

  • A disintegrin and metalloprotease 9 (ADAM9)
  • AKT
  • NF-κB
  • triple-negative breast cancer (TNBC)
  • tumor progression

ASJC Scopus subject areas

  • Medicine(all)

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