Regulation of ARL2 in colorectal cancer cell proliferation and tumorigenicity, and its negative association with AXL

Abstract

Colorectal cancer (CRC) is the third most common malignant disease in adults. ADP ribosylation factor-like GTPase 2 (ARL2) is crucial for controlling the dynamics of microtubules and mitochondrial functions. However, the biological function of ARL2 in CRC remains unclear. The present study was performed to identify the expression level and functional role of ARL2 in CRC. A total of 19 CRC and 3 normal healthy colorectal tissues were collected. Furthermore, ARL2 expression was analyzed in healthy colorectal and CRC tissues by immunohistochemistry (IHC). ARL2 overexpression and knockdown was achieved using lentiviral vectors and plasmid transfection in HCT8 and HCT116 cells. The protein and mRNA expression levels of ARL2 and AXL were analyzed using western blot and reverse transcription-quantitative PCR in ARL2 knockdown and ARL2 overexpressing HCT8 and HCT116 cells. Cell Counting Kit-8, colony formation, wound healing, and Matrigel assays were used to investigate the biological functions of ARL2. Taken together, ARL2 protein expression level was upregulated in CRC tissues. Furthermore, ARL2 overexpression decreased proliferation and weakened the colony-formation abilities of the CRC cells, as well as their migratory and invasive abilities. ARL2 interference enhanced proliferation and colony-formation rates of the CRC cells, as well as their migratory and invasive abilities. ARL2 regulated CRC proliferation and tumorigenicity and was negatively associated with AXL. The results of the present study suggested that the proliferation, migration and tumorigenicity of the CRC cells could be inhibited by ARL2 overexpression. The latter may be used as a predicted and potential therapeutic target for CRC.

ARL2 is required for homologous recombination repair and colon cancer stem cell survival

“…These roles, especially those in RAS activation and centrosome assembly, suggest a positive function of ARL2 in cancer or carcinogenesis. In recent years, interesting roles of ARL2 (both positive and negative) have been identified in cancer [ 7 , 8 , 9 , 10 ]. While ARL2 promotes proliferation in breast [ 7 ] and colon cancer [ 8 ], it suppresses proliferation in glioblastoma [ 10 ].…”

“…In recent years, interesting roles of ARL2 (both positive and negative) have been identified in cancer [ 7 , 8 , 9 , 10 ]. While ARL2 promotes proliferation in breast [ 7 ] and colon cancer [ 8 ], it suppresses proliferation in glioblastoma [ 10 ]. These interesting but contradictory roles of ARL2 observed in different studies are not fully explained by the known cellular function of ARL2, which suggests that there are still some significant biological functions of ARL2 to be identified.…”