Bennett, Richard D.

Myosin 10 (Myo10) is an unconventional myosin involved in a wide range of cell processes from filopodial formation and extension to spindle orientation during cell division. Among its multiple functional domains, Myo10 contains three IQ motifs that bind calmodulin and specifically calmodulin‐like protein (CLP) as light chains. We have recently shown that CLP expression up‐regulates Myo10, leading to increased Myo10‐dependent cell motility and filopodial extension (R.D. Bennett et al., J. Biol. Chem. 282, 3205–3212, 2007). CLP‐dependent Myo10 up‐regulation occurs without a concomitant increase in Myo10 mRNA. We followed Myo10 degradation in vivo and in vitro and found that CLP does not affect the decay rate of Myo10. Myo10 decayed rapidly with a half‐life of about 2.5 hours indicating that this myosin participates in signaling processes. Using an in vitro transcription/translation system we determined that CLP increased Myo10 heavy chain translation, resulting in a higher relative accumulation of Myo10 in the presence than in the absence of CLP. Taken together, our data suggest that CLP functions to increase translation of Myo10 possibly by acting as a chaperone for the emerging Myo10 heavy chain protein. Supported in part by the Mayo Graduate School and grant BCTR‐0201979 from the Susan G. Komen Breast Cancer Foundation.

Oral cancer is often diagnosed only at advanced stages due to a lack of reliable disease markers. The purpose of this study was to determine if the epithelial-specific human calmodulin-like protein (CALML3) could be used as marker for the various phases of oral tumor progression. Immunohistochemical analysis using an affinity-purified CALML3 antibody was performed on biopsy-confirmed oral tissue samples representing these phases. A total of 90 tissue specimens were derived from 52 patients. Each specimen was analyzed in the superficial and basal mucosal cell layers for overall staining and staining of cellular subcompartments. CALML3 was strongly expressed in benign oral mucosal cells with downregulation of expression as squamous cells progress to invasive carcinoma. Based on the Cochran-Armitage test for trend, expression in the nucleus and at the cytoplasmic membrane significantly decreased with increasing disease severity. Chi-square test showed that benign tissue specimens had significantly more expression compared to dysplasia/CIS and invasive specimens. Dysplasia/CIS tissue had significantly more expression than invasive tissue. We conclude that CALML3 is expressed in benign oral mucosal cells with a statistically significant trend in downregulation as tumorigenesis occurs. CALML3 may thus be a sensitive new marker for oral cancer screening.