RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.

Journal Article (Journal Article)

Epithelial-to-mesenchymal transition (EMT) is a critical underpinning process for cancer progression, recurrence and resistance to drug treatment. Identification of new regulators of EMT could lead to the development of effective therapies to improve the outcome of advanced cancers. In the current study we discovered, using a variety of in vitro and in vivo approaches, that RAB4A function is essential for EMT and related manifestation of stemness and invasive properties. Consistently, RAB4A suppression abolished the cancer cells' self-renewal and tumor forming ability. In terms of downstream signaling, we found that RAB4A regulation of EMT is achieved through its control of activation of the RAC1 GTPase. Introducing activated RAC1 efficiently rescued EMT gene expression, invasion and tumor formation suppressed by RAB4A knockdown in both the in vitro and in vivo cancer models. In summary, this study identifies a RAB4A-RAC1 signaling axis as a key regulatory mechanism for the process of EMT and cancer progression and suggests a potential therapeutic approach to controlling these processes.

Full Text

Duke Authors

Cited Authors

  • Karthikeyan, S; Casey, PJ; Wang, M

Published Date

  • October 28, 2022

Published In

Volume / Issue

  • 24 / 1

Start / End Page

  • 72 -

PubMed ID

  • 36307864

Pubmed Central ID

  • PMC9615386

Electronic International Standard Serial Number (EISSN)

  • 1465-542X

Digital Object Identifier (DOI)

  • 10.1186/s13058-022-01564-6


  • eng

Conference Location

  • England