A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion

Vijay Pralhad Kale, Jeremy A. Hengst, Dhimant H. Desai, Taryn E. Dick, Katherine N. Choe, Ashley L. Colledge, Yoshinori Takahashi, Shen Shu Sung, Shantu G. Amin, Jong K. Yun

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Two structurally related protein kinase families, the Rho kinases (ROCK) and the myotonic dystrophy kinase-related Cdc42-binding kinases (MRCK) are required for migration and invasion of cancer cells. We hypothesized that simultaneous targeting of these two kinase families might represent a novel therapeutic strategy to block the migration and invasion of metastatic cancers. To this end, we developed DJ4 as a novel small molecule inhibitor of these kinases. DJ4 potently inhibited activities of ROCK and MRCK in an ATP competitive manner. In cellular functional assays, DJ4 treatment significantly blocked stress fiber formation and inhibited migration and invasion of multiple cancer cell lines in a concentration dependent manner. Our results strongly indicate that DJ4 may be further developed as a novel anti-metastatic chemotherapeutic agent for multiple cancers.

Original languageEnglish (US)
Pages (from-to)299-310
Number of pages12
JournalCancer Letters
Volume354
Issue number2
DOIs
StatePublished - Nov 28 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion'. Together they form a unique fingerprint.

Cite this