Published online Apr 21, 2021. doi: 10.3748/wjg.v27.i15.1595
Peer-review started: January 21, 2021
First decision: February 9, 2021
Revised: February 17, 2021
Accepted: March 13, 2021
Article in press: March 13, 2021
Published online: April 21, 2021
Processing time: 82 Days and 21.1 Hours
Expression of the full-length isoform of Abelson interactor 1 (ABI1), ABI1-p65, is increased in colorectal carcinoma (CRC) and is thought to be involved in one or more steps leading to tumor progression or metastasis. The ABI1 splice isoform-L (ABI1-SiL) has conserved WAVE2-binding and SH3 domains, lacks the homeo-domain homologous region, and is missing the majority of PxxP- and Pro-rich domains found in full-length ABI1-p65. Thus, ABI1-SiL domain structure suggests that the protein may regulate CRC cell morphology, adhesion, migration, and metastasis via interactions with the WAVE2 complex pathway.
To investigate the potential role and underlying mechanisms associated with ABI1-SiL-mediated regulation of CRC.
ABI1-SiL mRNA expression in CC tissue and cell lines was measured using both qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. A stably ABI1-SiL overexpressing SW480 cell model was constructed using Lipofectamine 2000, and cells selected with G418. Image J software, CCK8, and transwell assays were used to investigate SW480 cell surface area, proliferation, migration, and invasion. Immunoprecipitation, Western blot, and co-localization assays were performed to explore intermolecular interactions between ABI1-SiL, WAVE2, and ABI1-p65 proteins.
ABI1-SiL was expressed in normal colon tissue and was significantly decreased in CRC cell lines and tissues. Overexpression of ABI1-SiL in SW480 cells significantly increased the cell surface area and inhibited the adhesive and migration properties of the cells, but did not alter their invasive capacity. Similar to ABI1-p65, ABI1-SiL still binds WAVE2, and the ABI1-p65 isoform in SW480 cells. Furthermore, co-localization assays confirmed these intermolecular interactions.
These results support a model in which ABI1-SiL plays an anti-oncogenic role by competitively binding to WAVE2 and directly interacting with phosphorylated and non-phosphorylated ABI1-p65, functioning as a dominant-negative form of ABI1-p65.
Core Tip: The purpose of this study was to investigate the role and mechanism of Abelson interactor 1 splice isoform-L (ABI1-SiL) in the metastatic behavior of colorectal carcinoma cells. Our results showed that ABI1-SiL played a key role in cell surface area, adhesion, and migration, but not in proliferation and apoptosis in SW480 cells. ABI1-SiL may have anti-oncogenic roles by competitively binding to WAVE2, and directly interacting with phosphorylated and non-phosphorylated ABI1-p65, functioning as a dominant-negative molecule towards ABI1-p65.