Loss of phosphatase and tensin homolog (PTEN) increases Lysyl oxidase-like 2 (LOXL2) expression enhancing the growth of fallopian tube epithelial cells as three-dimensional spheroids

• DOI: 10.1016/j.cpt.2024.03.003
• Publication Date: 2024-03-26T17:34:33Z
• Authors: Angela Russo; Junlone Moy; Manead Khin; Timothy R. Dorsey; Alfredo Lopez Car...; Joanna E. Burdette
• Keywords: Tensin; Lysyl Oxidase; Fallopian tube; Spheroid

High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of all cancer-related deaths. Multiple studies have suggested that the fallopian tube epithelium (FTE) serves as cell origin HGSOC. Phosphatase and tensin homolog (PTEN) is a tumor suppressor its loss sufficient to induce numerous tumorigenic changes in FTE, including increased migration, formation multicellular spheroids (MTSs), colonization. In murine oviductal epithelial (MOE) cells (the equivalent human FTE) PTEN results upregulation transcripts associated with extracellular matrix, specific focus on elevation lysyl oxidase-like 2 (LOXL2). Although LOXL2 known drive transformation invasion solid tumors poor prognosis cancer, role tumorigenesis originating from FTE remains unclear. Therefore, we aim investigate whether mediates epithelium. this study, utilized clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (CAS9) technology delete PTEN-deficient MOE understand mediating oncogenic effects loss. addition, CRISPR-CAS9 was used OVCAR8 cells. We monitored properties, such invasion, growth three-dimensional (3D) spheroids, assess resulted any changes. found reduction expression did not significantly change migration or invasive capabilities PTEN-depleted However, significant 3D MTS survival both lines. These reveal first time increases through downregulation Pax2, deletion blocks spheroid formation.