ADAM10 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the A2780 human ovarian carcinoma cell line, featuring CRISPR/Cas9-mediated gene disruption of the ADAM10 gene. This loss-of-function model enables investigation of ADAM10’s role in ectodomain shedding and related signaling pathways without clonal variation. The polyclonal format provides a heterogeneous knockout pool representing diverse genetic edits, suitable for functional studies where averaging over the population captures consistent biological effects.
The A2780 cell line is an epithelial ovarian cancer model established from an untreated patient, characterized by wild-type TP53 and sensitivity to cisplatin. Its epithelial morphology and genetic stability make it a preferred system for studying ovarian cancer biology, drug responses, and mechanisms of chemoresistance. The A2780 background retains functional signaling pathways relevant to cell adhesion, migration, and proliferation, providing a physiologically pertinent context for assessing ADAM10 loss.
ADAM10 encodes a transmembrane metalloprotease that functions as an ectodomain sheddase, cleaving substrates such as Notch receptors, amyloid precursor protein (APP), E-cadherin, and N-cadherin. This shedding regulates Notch signaling by cleaving Notch1 to release the Notch intracellular domain (NICD), which activates Hes/Hey target genes via RBP-J. ADAM10 shedding of E-cadherin modulates cell-cell adhesion and ??-catenin signaling, while cleavage of APP generates sAPP??. ADAM10 activity is regulated by hypoxia, growth factors, and calcium influx, and is inhibited by TIMP-1 and TIMP-3. It interacts with TspanC8 tetraspanins, ADAM17, and the ??-secretase complex.
In ovarian cancer, ADAM10 knockout disrupts proteolytic processing of key substrates, impairing Notch signaling and cell adhesion, leading to reduced proliferation, migration, and tumorigenic potential. The A2780 background, with wild-type TP53 and cisplatin sensitivity, provides a clean model to dissect ADAM10-dependent pathways. Disruption of ADAM10-mediated shedding may also affect EGFR and TNF-?? signaling, linked to ovarian cancer progression. This model enables exploration of how loss of ectodomain shedding influences oncogenic signaling and therapeutic responses.
Applications include investigating Notch signaling dynamics via Western blotting for NICD and RT-qPCR for Hes1/Hey1, assessing cell adhesion using E-cadherin immunoblotting and adhesion assays, and evaluating migration/invasion through Transwell assays. The model can be used to study drug resistance mechanisms by combining cisplatin sensitivity assays with apoptosis analysis by flow cytometry, and to perform RNA-seq to capture transcriptomic changes upon ADAM10 loss. Additional applications include EMT studies, ectodomain shedding characterization, and screening for modulators of ADAM10-dependent pathways. For further information or to discuss custom applications, please contact Ascent Research.
