Mechanism and biological significance of CD44 cleavage

Osamu Nagano, Hideyuki Saya

Research output: Contribution to journalReview articlepeer-review

309 Citations (Scopus)


There are multiple steps in the metastasis of cancer cells. Tumor cells must first detach from the tumor mass and invade the surrounding extracellular matrix (ECM). In this step, cell surface adhesion molecules play an important role in the interaction between the cells and their microenvironments. CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and is implicated in a wide variety of physiological and pathological processes. Recently, proteolytic cleavages of CD44 have been emerging as key regulatory events for the CD44 dependent cell-matrix interaction and signaling pathway. CD44 undergoes sequential proteolytic cleavages in the ectodomain and intramembranous domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. The ectodomain cleavage of CD44 is triggered by multiple stimulations and contributes to the regulation of cell attachment to and migration on HA matrix. The ectodomain cleavage subsequently induces the intramembranous cleavage, which is mediated by presenilin (PS)-dependent γ-secretase. The intramembranous cleavage generates CD44ICD, which acts as a signal transduction molecule; it is translocated to the nucleus and activates transcription. An understanding of the underlying mechanism of these cleavages of CD44 could provide novel therapeutic targets for cancer cell invasion and metastasis.

Original languageEnglish
Pages (from-to)930-935
Number of pages6
JournalCancer science
Issue number12
Publication statusPublished - 12-2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Dive into the research topics of 'Mechanism and biological significance of CD44 cleavage'. Together they form a unique fingerprint.

Cite this