title: Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway.
abstract: OBJECTIVE
  HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions. Recent studies have shown that the FoxO transcription factors play a pivotal role during cancer progression. Here, we explored the correlation between HepaCAM and the FoxO family via regulation of the PI3K/AKT pathway.
  
  
  METHODS
  HepaCAM and FoxO3 expression were detected by immunohistochemistry staining. We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting. We observed the nuclear translocation of FoxO3 by immunofluorescence staining after expressing HepaCAM.
  
  
  RESULTS
  HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3. Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression. We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression. Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79. Moreover, we observed that HepaCAM induced nuclear translocation of FoxO3.
  
  
  CONCLUSIONS
  Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
authors.affiliation: The Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.affiliation: The Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Nanjing
authors.initials: N
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Quan
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Xiaohou
authors.initials: X
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China. luochunli79@126.com.
authors.forename: Chunli
authors.initials: C
authors.lastname: Luo
mesh_terms: D018797:Cell Cycle Proteins; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071316:Forkhead Box Protein O3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; D002867:Chromones; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; C487620:HEPACAM protein, human; D009025:Morpholines; D011506:Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Bladder carcinoma; Cell proliferation; HepaCAM; p-FoxO1/3