title: Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells.
abstract: Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression.
authors.affiliation: Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 8128582, Japan.
authors.forename: Tomoki
authors.identifier: http://orcid.org/0000-0002-8027-9923
authors.initials: T
authors.lastname: Sumida
authors.affiliation: Department of Oral & Maxillofacial Surgery, Ehime University Graduate School of Medicine, 454, Shitsukawa, Toon, 7910295, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishikawa
authors.affiliation: Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 8128582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 8128582, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 8128582, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mori
authors.affiliation: California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, Suite 220, San Francisco, California, 94107, USA.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Desprez
mesh_terms: D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014746:Vimentin