title: Modification of cysteine 457 in plakoglobin modulates the proliferation and migration of colorectal cancer cells by altering binding to E-cadherin/catenins.
abstract: OBJECTIVE
  In tissue samples from patients with colorectal cancer (CRC), oxidation of C420 and C457 of plakoglobin (Pg) within tumor tissue was identified by proteomic analysis. The aim of this study was to identify the roles of Pg C420 and C457.
  
  
  METHODS
  Human CRC tissues, CRC and breast cancer cells, and normal mouse colon were prepared to validate Pg oxidation. MC38 cells were co-transfected with E-cadherin plus wild type (WT) or mutant (C420S or C457S) Pg to evaluate protein interactions and cellular localization, proliferation, and migration.
  
  
  RESULTS
  Pg was more oxidized in stage III CRC tumor tissue than in non-tumor tissue. Similar oxidation of Pg was elicited by H2O2treatment in normal colon and cancer cells. C457S Pg exhibited diminished binding to E-cadherin and α-catenin, and reduced the assembly of E-cadherin-α-/β-catenin complexes. Correspondingly, immunofluorescent analysis of Pg cellular localization suggested impaired binding of C457S Pg to membranes. Cell migration and proliferation were also suppressed in C457S-expressing cells.
  
  
  CONCLUSIONS
  Pg appears to be redox-sensitive in cancer, and the C457 modification may impair cell migration and proliferation by affecting its interaction with the E-cadherin/catenin axis. Our findings suggest that redox-sensitive cysteines of Pg may be the targets for CRC therapy.
authors: a Department of Oral Biochemistry , Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University , Gwangju , Republic of Korea.|b Department of Molecular Medicine (BK21plus) , Chonnam National University Graduate School , Gwangju , Republic of Korea.
authors: Suhee
authors: http://orcid.org/0000-0002-9315-0360
authors: S
authors: Kim
authors: a Department of Oral Biochemistry , Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University , Gwangju , Republic of Korea.
authors: Sun Hee
authors: http://orcid.org/0000-0002-0772-9588
authors: SH
authors: Ahn
authors: a Department of Oral Biochemistry , Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University , Gwangju , Republic of Korea.
authors: Hee-Young
authors: http://orcid.org/0000-0001-7654-8708
authors: HY
authors: Yang
authors: a Department of Oral Biochemistry , Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University , Gwangju , Republic of Korea.
authors: Jin-Sil
authors: http://orcid.org/0000-0002-9795-3128
authors: JS
authors: Lee
authors: a Department of Oral Biochemistry , Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University , Gwangju , Republic of Korea.|b Department of Molecular Medicine (BK21plus) , Chonnam National University Graduate School , Gwangju , Republic of Korea.
authors: Hyang-Gi
authors: http://orcid.org/0000-0001-7487-4585
authors: HG
authors: Choi
authors: c Department of Surgery , Chonnam National University Hwasun Hospital , Hwasun , Republic of Korea.
authors: Young-Kyu
authors: http://orcid.org/0000-0002-3009-404X
authors: YK
authors: Park
authors: a Department of Oral Biochemistry , Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University , Gwangju , Republic of Korea.|b Department of Molecular Medicine (BK21plus) , Chonnam National University Graduate School , Gwangju , Republic of Korea.
authors: Tae-Hoon
authors: http://orcid.org/0000-0003-0105-1750
authors: TH
authors: Lee
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011485:Protein Binding; D051185:gamma Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051177:Catenins; D051185:gamma Catenin; D006861:Hydrogen Peroxide
keywords: Colorectal cancer; E-cadherin; cysteine; oxidation; plakoglobin