Targeting Rho GTPase Signaling Networks in Cancer

Natasha S Clayton, Anne J Ridley*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

83 Downloads (Pure)

Abstract

As key regulators of cytoskeletal dynamics, Rho GTPases coordinate a wide range of cellular processes, including cell polarity, cell migration, and cell cycle progression. The adoption of a pro-migratory phenotype enables cancer cells to invade the stroma surrounding the primary tumor and move toward and enter blood or lymphatic vessels. Targeting these early events could reduce the progression to metastatic disease, the leading cause of cancer-related deaths. Rho GTPases play a key role in the formation of dynamic actin-rich membrane protrusions and the turnover of cell-cell and cell-extracellular matrix adhesions required for efficient cancer cell invasion. Here, we discuss the roles of Rho GTPases in cancer, their validation as therapeutic targets and the challenges of developing clinically viable Rho GTPase inhibitors. We review other therapeutic targets in the wider Rho GTPase signaling network and focus on the four best characterized effector families: p21-activated kinases (PAKs), Rho-associated protein kinases (ROCKs), atypical protein kinase Cs (aPKCs), and myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs).
Original languageEnglish
Article number222
Number of pages12
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - 3 Apr 2020

Keywords

  • Cancer
  • GTPase
  • invasion
  • metastasis
  • Rho

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