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• W4362595890 abstract "Abstract The primary cause of cancer-associated death is due to the development of metastatic disease. Metastasis is a multistage process requiring displacement of cells from the primary tumor, survival in circulation, and adhesion and growth in a secondary location. Reorganization of both the actin and microtubule cytoskeleton is critical for metastasis of solid tumors. Drugs that inhibit microtubule dynamics, including microtubule stabilizers and destabilizers, are used to treat metastatic breast cancer, however there is no rationale to guide the choice among these drugs. Septins, a class of small GTPases, interact with both microtubules and actin to functionally link these cytoskeletal components. Expression of a specific isoform, septin9_i1, is associated with breast cancer development, migration, and drug resistance. This isoform is unique among septins in that it contains a specific microtubule binding domain required for association of septins with microtubules. We found that microtubule stabilizing or destabilizing chemotherapeutics currently used to treat metastatic breast cancer promoted respective microtubule or actin localization of oncogenic septins, particularly when septin9_i1 was expressed. This differential cellular distribution correlated with our finding that microtubule destabilizers were more effective than stabilizers at inhibiting the migration of septin9_i1 expressing breast cancer cells in vitro whereas the drugs were equally effective in isogenic cells depleted of septin9_i1. We are currently testing the hypothesis that septin9_i1 promotes in vivo metastasis of breast tumors and that microtubule destabilizers will be more effective than stabilizers at inhibiting this metastasis. This supports our ongoing clinical investigations to determine whether septin9_i1 expression could be used as a predictive biomarker to guide the selection among microtubule-targeted chemotherapeutics, which is significant as there is currently no molecular guidance to inform on this choice. Our findings will promote the more targeted and rational use of this highly used but mechanistically underappreciated class of chemotherapy. Citation Format: Jacob N. Essif, Samantha S. Yee, April Risinger. Septin isoform expression as a potential biomarker for differential response to microtubule targeted chemotherapy in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2185." @default.
• W4362595890 created "2023-04-06" @default.
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• W4362595890 date "2023-04-04" @default.
• W4362595890 modified "2023-09-25" @default.
• W4362595890 title "Abstract 2185: Septin isoform expression as a potential biomarker for differential response to microtubule targeted chemotherapy in breast cancer" @default.
• W4362595890 doi "https://doi.org/10.1158/1538-7445.am2023-2185" @default.
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