Carcinoembryonic antigen related cell adhesion molecule 6 promotes the proliferation and migration of renal cancer cells through the ERK/AKT signaling pathway

Rujian Zhu, Jiong Ge, Junjie Ma, Junhua Zheng


Background: Carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6) is a versatile glycoprotein and a member of the CEACAM family. Studies suggested that it served as a diagnostic and prognostic biomarker in some malignancies. In addition, it is involved in tumorigenesis by stimulating proliferation, suppressing apoptosis, facilitating migration and invasion, promoting angiogenesis, and inducing drug resistance. In the present study, we demonstrated the oncogenic effects of CEACAM6 in clear cell renal cell carcinoma (ccRCC).
Methods: CEACAM6 expression was detected by quantitative real-time PCR (qRT-PCR), immunohistochemical staining and western blot in ccRCC tumor tissues and cell lines. Survival analysis was performed using the data of TCGA database. Cell proliferation and migration were detected by CCK-8 and transwell assays with the overexpression or silencing of CEACAM6. LY294002 was used to block the activation of PI3K/AKT pathway. Associated pathway proteins were detected by western blot.
Results: CEACAM6 was upregulated in ccRCC cell lines and tumor tissues. Longer overall survival was observed in patients with relatively low CEACAM6 levels. Furthermore, overexpression of CEACAM6 promoted the proliferation and migration of ccRCC cells. Conversely, shRNA-mediated CEACAM6 depletion modulated those changes. Further investigation demonstrated that the ERK/AKT signaling pathway activation played a pivotal role. In addition, PI3K/AKT pathway blockade abrogated the effects of CEACAM6 overexpression.
Conclusions: Aberrantly high expression of CEACAM6 is a stimulus for the formation and progression of ccRCC.