title: PKA RIα/A-kinase anchoring proteins 10 signaling pathway and the prognosis of colorectal cancer.
abstract: OBJECTIVE
  Previously study showed that the loss of the control of cAMP-dependent protein kinase A RIα (PKA RIα)/ A-kinase anchoring proteins 10 (AKAP10) signaling pathway initiate dysregulation of cellular healthy physiology leading to tumorigenesis. The aim of this study was to investigate the role of PKA RIα/AKAP10 signaling pathway in colorectal cancer (CRC).
  
  
  METHODS
  The AKAP10 expression at the mRNA and protein level have been analyzed in colon cancer cell lines, primary CRCs and matched normal mucosa samples, and compared in accordance with specific clinicopathological features of CRC. The correlation between expression of AKAP10 and PKA RIα were also analyzed.
  
  
  RESULTS
  Compared with HCT116 and SW480 cells, the AKAP10 was significantly upregulated in the colon cell line KM12C and its metastatic counterparts, KM12SM and KM12L4A. Moreover, the KM12SM and KM12L4A having high metastatic potentials displayed the elevated levels of AKAP10 compared with KM12C having poor metastatic potential. A notably higher level of AKAP10 expression was found in CRC tissues at both mRNA and protein levels. Increased expression of AKAP10 in CRC patients was positively associated with the depth of invasion and the grade of differentiation. Univariate survival analysis showed that the increased expression of AKAP10 was related to poorer survival. Cox multivariate regression analysis confirmed that AKAP10 was an independent predictor of the overall survival of CRC patients. PKA RIα mRNA was also expressed at high levels in CRC. The correlation coefficient between mRNA expression of AKAP10 and PKA RIα in CRC was 0.417. AKAP10 mRNA overexpression was correlated significantly with PKA RIα.
  
  
  CONCLUSIONS
  Our data indicated that PKA RIα/AKAP10 signaling pathway is associated with the progression and prognosis of CRC.
authors.affiliation: Department of Gastrointestinal Surgery, Institute of Digestive Surgery, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Mojin
authors.initials: M
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Keling
authors.initials: K
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics* / Q000502:physiology*; D000368:Aged; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics* / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D013534:Survival; D015854:Up-Regulation / Q000235:genetics
chemical_list: D054758:A Kinase Anchor Proteins; C484639:AKAP10 protein, human; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D012333:RNA, Messenger
keywords: PKA RIα/AKAP10 signaling pathway; colorectal cancer (CRC); prognosis