The APLP2 Knockout HT29 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HT29 human colorectal adenocarcinoma cell line, in which the APLP2 gene has been disrupted. This loss-of-function model enables investigation of APLP2-dependent biological processes.
HT29 cells are a widely utilized in vitro model originating from a primary colorectal adenocarcinoma, retaining key features of intestinal epithelial cells including polarized organization, secretory activity, and absorptive functions. They are commonly employed in studies of colorectal cancer progression, epithelial differentiation, and mucosal barrier biology.
APLP2 is a type I transmembrane protein of the APP family. It undergoes sequential alpha- and gamma-secretase cleavage, releasing an intracellular domain (AICD) that translocates to the nucleus and forms a transcriptional complex with Fe65 (APBB1) and Tip60. This complex regulates genes such as neprilysin (NEP), BACE1, and GSK3B. APLP2 also participates in copper homeostasis by binding copper ions and modulating transporters CTR1 and ATP7A. Moreover, APLP2 mediates cell adhesion through interactions with integrins and the scaffolding protein X11/Mint (APBA1). As a gamma-secretase substrate, its processing competes with Notch receptors, connecting APLP2 to Notch signaling.
In the HT29 colorectal cancer setting, disruption of APLP2 expression may alter cell-extracellular matrix interactions, migratory capacity, and proliferation. The loss of this gamma-secretase substrate can shift the balance of enzyme availability toward other cleavages, potentially impacting Notch signaling and other pathways dependent on gamma-secretase activity. Given that HT29 cells are of intestinal epithelial origin, APLP2 knockout also provides a relevant platform for studying copper metabolism in the gut and its implications for tumor cell behavior.
Research applications encompass colorectal cancer biology, gamma-secretase substrate competition studies, cell adhesion and migration analyses, copper homeostasis investigation, and drug target validation for Alzheimer’s pathways. Compatible assays include Western blotting, qRT-PCR, wound healing and transwell assays, MTT and colony formation proliferation assays, gamma-secretase activity assays, co-immunoprecipitation of the AICD-Fe65-Tip60 complex, RNA-seq, and immunofluorescence. Please contact Ascent Research for further details.
