Defining the role of ABI1 in cancer progression and metastasis
Abl Interactor 1 (ABI1)
Abelson Interactor 1 (ABI1), originally known as Spectrin SH3 Domain binding protein 1, is a multifunctional adaptor/scaffolding protein with roles in actin polymerization, tyrosine kinase regulation and cancer progression. As a member of WAVE and WASP regulatory complexes, ABI1 acts to regulate cellular processes such as cell motility, cell spreading, endocytosis, cell adhesion, and cell division. As a tyrosine kinase regulator, ABI1 is known to regulate SRC family kinases and Abl. Additionally, ABI1 has roles in the regulation of macropinocytosis and embryonic development. Recent work in our lab identified ABI1 as a tumor suppressor in prostate cancer. Loss of ABI1 leads to epithelial-mesenchymal transition (EMT) through activation of the FYN-STAT3 axis downstream of non-canonical Wnt signaling. The goal of our research is to determine the role of ABI1 in tumor progression.
RWPE-1 3D organoid
ABI1 KO RWPE-1 3D organoid
Prostate cancer is one of the most critical healthcare issues in the United States with around 180,000 new cases and 30,000 deaths every year. Prostate cancer is progressive, eventually leading to an aggressive and metastatic disease resistant to anti-androgen therapy. Recent findings from our lab showed that ABI1 loss promotes epithelial-mesenchymal transition (EMT) in prostate cancer, a key mechanism underlying prostate cancer progression. Work in our lab focuses on understanding the underlying mechanism of prostate cancer progression and how current treatments select for a more metastatic and aggressive disease state through loss of ABI1.
Nath et al., 2019. Cell Commun Signal. 2019 Sep 18;17(1):120. doi: 10.1186/s12964-019-0410-y
Breast cancer (BCa) causes significant morbidity and mortality with an estimated 250,000 new cases and 40,000 deaths per year in the US. Although the overall number of deaths from breast cancer decreased over the last decade, mortality remains high for patients with invasive disease.
The long-term goal of our breast cancer research is elimination of mortality from invasive breast cancer through development of personalized targeted therapies, with the focus on understanding of ABI1 in metastatic progression of breast cancer. ABI1 is one of the major components of WAVE complex. ABI1-WAVE complex is amplified or overexpressed in over 30% of invasive breast cancers and associated with early recurrence and increased risk of mortality. Thus, we postulate that overexpression of Abi1 plays an oncogenic role in human breast cancer. We developed an innovative research approach, which utilizes our unique Abi1 KO mouse model, gene editing, somatic tissue engineering, and single cell RNA sequencing of tumors to understand the role of ABI1 in breast cancer.