The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

Sci Rep. 2021 May 24;11(1):10734. doi: 10.1038/s41598-021-90220-8.

Abstract

Abnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Alternative Splicing
  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Neoplasm Transplantation
  • Phosphorylation
  • Prognosis
  • Up-Regulation

Substances

  • ABI1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • EPS8 protein, human