A peptide includes SEQ ID NO:3, substitution and addition variants thereof which maintain the ability to activate CD44. A complex includes this peptide or an Å6 polypeptide with a CD44 polypeptide. An isolated polypeptide includes the Link region sequence of human CD44, functionally active fragments thereof, substitution variants, and addition variants. A method of treating a disease characterized by aberrant cell migration and/or invasion includes administering to a subject an effective amount of the peptide of SEQ ID NO:3 or an Å6 polypeptide to bind to a CD44 polypeptide and modulate signal transduction activity for a sufficient period of time to treat the disease. Other methods include using the peptide of SEQ ID NO:3 or an Å6 polypeptide for diagnosing, identifying a subpopulation of subjects responsive to treatment, and screening for compounds that bind a CD44 polypeptide.