Correlation of ABI1 and PTEN expression during prostate tumor progression

• Published in: Journal of clinical oncology Vol. 40; no. 6_suppl; p. 172
• Main Authors: Kotula, Leszek, Hryniewicz-Jankowska, Anita, Li, Xiang, Augoff, Katarzyna, Papp, Csaba, Das, Disharee, Kung, Sonia H.Y., Fazli, Ladan, Jasmaspishvili, Tamara, Berman, David Monty, Zhang, Fan, Porter, Baylee, Sikorski, Aleksander, Gleave, Martin, Kuznetsov, Vladimir, Bratslavsky, Gennady
• Format: Journal Article
• Language: English
• Published: 20.02.2022
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2022.40.6_suppl.172

Abstract only 172 Background: Mechanisms of tumor invasion are not well defined. PTEN, a key tumor suppressor frequently inactivated in epithelial cancers, acts as a central node that controls tumor invasion. Despite PI-3 kinase-phospho-Akt pathway activation resulting in enhanced tumor growth, prostate tumors with PTEN loss undergo p53-mediated senescence that restricts tumor invasion. Methods: ABI1 downregulation is associated with epithelial-mesenchymal transition in highly invasive prostate tumors; these tumors frequently loose PTEN; therefore we set to examine genetic interaction of ABI1 and PTEN using novel mouse model of prostate cancer. We analyzed the correlation of ABI1 and PTEN expression in human PCa tumor tissue. Results: Here, using Abi1/Pten KO mouse model we identified a novel mechanism that guards tumor invasion. In Pten-null tumors upregulation of Abi1 leads to sequestration of activated Src kinase. In the absence of Abi1, this regulation is lost leading to activation of non-canonical WNT-SRC-STAT3 axis and enhanced invasion through activation of MMP2 activity. This molecular mechanism explains progression of tumors with Pten loss from PIN to invasive carcinoma upon concomitant Abi1 inactivation. In human tumors with low Abi1 and Pten are associated with aggressive phenotype, biochemical recurrence and metastasis. Conclusions: ABI1 acts as failsafe mechanism in PTEN null tumors by restricting SRC-mediated tumor invasion. ABI1 might have a predictive value in clinical setting in context of PTEN levels.