The immunoglobulin-like cell adhesion molecule hepaCAM is cleaved in the human breast carcinoma MCF7 cells.
We previously reported the identification and characteristics of hepaCAM, a new immunoglobulin-like adhesion molecule. Frequently lost in diverse tumors, hepaCAM exhibits antiproliferative effects on cancer cells and promotes cell-extracellular matrix (ECM) interactions when re-expressed. Herein, we demonstrate for the first time that hepaCAM is cleaved in the human breast carcinoma MCF7 cells, generating a fragment containing mainly the cytoplasmic domain. The phorbol ester phorbol 12-myristate 13-acetate (PMA) did not affect the cleavage of hepaCAM. However, calcium-influx promoted hepaCAM cleavage independent of PKC. In addition, inhibitors of proteasome and cysteine proteases strongly suppressed the cleavage of hepaCAM, indicating the involvement of proteasome, calpain-1 and cathepsin B. Furthermore, we showed that functions of hepaCAM were impaired when the cytoplasmic domain was cleaved. The truncation mutant of hepaCAM failed to promote cell-ECM adhesion and migration, and lost the inhibitory effects on cell growth, suggesting a regulatory role of the cleavage in hepaCAM functions.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore.
Ting
T
Zhang
Mei C
MC
Moh
Lay H
LH
Lee
Shali
S
Shen
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008954:Models, Biological; D008970:Molecular Weight; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; C487620:HEPACAM protein, human; D007136:Immunoglobulins; D061988:Proteasome Inhibitors; D020033:Protein Isoforms; D011506:Proteins; C016658:phorbolol myristate acetate; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium