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ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence
Flavia R M Latini1, Jefferson P Hemerly, Beatriz C G Freitas
1Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics and Division of Endocrinology, Universidade Federal de São Paulo, SP, Brazil.
Background:
Mounting evidence has indicated that ABI3 (ABI family member 3) function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown.
Methods:
The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP). We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent.
Results:
We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression.
Conclusions:
Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.
Insights
ABI3 (ABI family member 3) acts as a tumor suppressor, with reduced expression in many carcinomas. Restoring ABI3 inhibits tumor growth and promotes senescence, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Growing evidence suggests ABI3 (ABI family member 3) functions as a tumor suppressor.
- The precise molecular mechanisms of ABI3's tumor-suppressive role are not fully understood.
Purpose of the Study:
- To investigate ABI3 expression in thyroid tumors.
- To explore the correlation between ABI3 and ABI3-binding protein (ABI3BP).
- To determine the biological effects of ABI3 reintroduction in cancer cell lines.
Main Methods:
- Analyzed ABI3 expression in benign and malignant thyroid tumors.
- Assessed ABI3 and ABI3BP expression correlation.
- Studied the impact of ectopic ABI3 expression on thyroid and colon cancer cell lines.
Main Results:
- ABI3 expression is frequently reduced or lost in carcinomas.
- ABI3 and ABI3BP expression show a positive correlation.
- Ectopic ABI3 expression suppressed tumor growth, reduced transforming activity, and increased cellular senescence, associated with p21 WAF1 upregulation and decreased ERK/E2F1.
Conclusions:
- ABI3 is linked to the pathogenesis and progression of certain cancers.
- ABI3 and its associated pathways represent potential therapeutic targets.
- Further characterization of ABI3-mediated pathways is warranted.
