CEACAM1 long isoform has opposite effects on the growth of human mastocytosis and medullary thyroid carcinoma cells.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in a number of tumor cell types. The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing isoforms of this molecule which possess a long cytoplasmic tail (CEACAM1-L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and/or SHP-2. Src family kinases (SFKs) are also known to bind to and phosphorylate CEACAM1-L isoforms. Here, we report that CEACAM1 was uniquely expressed at high levels in both human neoplastic mast cells (mastocytosis) and medullary thyroid carcinoma cell (MTC) lines, when compared with their expression in nonneoplastic mast cells or nonneoplastic C cells. This expression was mainly derived from CEACAM1-L isoforms based upon assessment of CEACAM1 mRNA expression. CEACAM1 knockdown upregulated cell growth of HMC1.2 cells harboring KIT mutations detected in clinical mastocytosis, whereas downregulated the growth of TT cells harboring RET mutations detected in clinical MTCs. Immunoblotting, ELISA and immunoprecipitaion analysis showed that activated SHP-1 is preferentially associated with CEACAM1 in HMC1.2 cells harboring KIT mutations, whereas Src family kinases (SFKs) are preferentially associated with CEACAM1 in TT cells harboring RET mutations. These studies suggest that the dominantly interacting proteins SHP1 or SFK determine whether CEACAM1-L displays a positive or negative role in tumor cells.
Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan.
Chiyuki
C
Ueshima
Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan.
Tatsuki R
http://orcid.org/0000-0003-3095-8976
TR
Kataoka
Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan.
Yusuke
Y
Takei
Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan.
Masahiro
M
Hirata
Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan.
Akihiko
A
Sugimoto
Department of Diagnostic Pathology, Kuma Hospital, Hyogo, Japan.
Mitsuyoshi
M
Hirokawa
Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan.
Yoshimichi
Y
Okayama
Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Richard S
RS
Blumberg
Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan.
Hironori
H
Haga
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019169:Jurkat Cells; D020014:K562 Cells; D008297:Male; D008415:Mastocytosis / Q000378:metabolism*; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D013964:Thyroid Neoplasms / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D019061:src-Family Kinases / Q000378:metabolism*
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D020033:Protein Isoforms; D019061:src-Family Kinases; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
CEACAM1; SHP-1; Src family kinases; mast cell; medullary thyroid carcinoma