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.
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.
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.
Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
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We thank the patients and their families who generously donated valuable tissue samples.
Conflict of interest
The authors declare no conflict of interest.
This study was supported by grants from the National Natural Science Foundation of China (NSFC) (Grant No. 81072086).
All of the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Ethics Committee of Chongqing Medical University.
Informed consent was obtained from all individual participants included in the study.
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Tang, M., Zhao, Y., Liu, N. et al. Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway. J Cancer Res Clin Oncol 143, 793–805 (2017). https://doi.org/10.1007/s00432-016-2333-y
- Bladder carcinoma
- Cell proliferation