The PKA RI alpha/A-kinase anchoring proteins 10 signaling pathway and the prognosis of colorectal cancer

• Background and AimPreviously study showed that the loss of the control of cAMP-dependent protein kinase A RI (PKA RI)/ 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 RI/AKAP10 signaling pathway in colorectal cancer (CRC). MethodsThe 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 RI were also analyzed. ResultsCompared 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 RI mRNA was also expressed at high levels in CRC. The correlation coefficient between mRNA expression of AKAP10 and PKA RI in CRC was 0.417. AKAP10mRNA overexpression was correlated significantly with PKA RI. ConclusionsOur data indicated that PKA RI/AKAP10 signaling pathway is associated with the progression and prognosis of CRC.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

colorectal cancer (CRC); PKA RI; AKAP10 signaling pathway; prognosis

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