BHMPS Inhibits Breast Cancer Migration and Invasion by Disrupting Rab27a‐Mediated EGFR and Fibronectin Secretion

Jeong In Park, Kyung Hee Song, Seong Mook Kang, Jeeyong Lee, Seong Jun Cho, Hyun Kyung Choi, Jiyeon Ahn, Jong Kuk Park, Jaesung Kim, Sang Gu Hwang, Dae Seog Lim, Joon Kim, Seung Youn Jung, Jie Young Song

Research output: Contribution to journalArticlepeer-review

Abstract

Our previous work demonstrated that (E)‐N‐benzyl‐6‐(2‐(3, 4‐dihydroxybenzylidene) hydrazinyl)‐N‐methylpyridine‐3‐sulfonamide (BHMPS), a novel synthetic inhibitor of Rab27aSlp(s) interaction, suppresses tumor cell invasion and metastasis. Here, we aimed to further investigate the mechanisms of action and biological significance of BHMPS. BHMPS decreased the expression of epithelial‐mesenchymal transition transcription factors through inhibition of focal adhesion kinase and c‐Jun N‐terminal kinase activation, thereby reducing the migration and invasion of breast cancer. Additionally, knockdown of Rab27a inhibited tumor migration, with changes in related signaling molecules, whereas overexpression of Rab27a reversed this phenomenon. BHMPS effectively prevented the interaction of Rab27a and its effector Slp4, which was verified by co‐localization, immunoprecipitation, and in situ proximity ligation assays. BHMPS decreased the secretion of epidermal growth factor receptor and fibronectin by interfering with vesicle trafficking, as indicated by increased perinuclear accumulation of CD63‐positive vesicles. Moreover, administration of BHMPS suppressed tumor growth in Rab27a‐overexpressing MDA‐MB‐231 xenograft mice. These findings suggest that BHMPS may be a promising candidate for attenuating tumor migration and invasion by blocking Rab27a‐mediated exocytosis.

Original languageEnglish
Article number373
JournalCancers
Volume14
Issue number2
DOIs
Publication statusPublished - 2022 Jan 1

Keywords

  • Breast cancer
  • Invasion
  • Migration
  • Rab GTPase
  • Vesicle trafficking

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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