The HCFC1R1 Knockout 143B Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population of the 143B human osteosarcoma cell line with targeted disruption of the HCFC1R1 (HPIP/PBXIP1) gene. This genetically heterogeneous pool of knockout cells provides a physiologically relevant model for studying loss-of-function effects without the clonal selection biases associated with single-cell-derived lines. The polyclonal format is designed for functional genomics, oncogenic signaling dissection, and preclinical drug target validation.
The parental 143B cell line is a widely characterized human osteosarcoma model originally derived from a patient tumor and selected for thymidine kinase and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency. Exhibiting fibroblast-like morphology, 143B cells are routinely employed in tumorigenesis and metastasis research, including xenograft tumor growth and gene expression analyses, owing to their aggressive phenotype and molecular similarity to high-grade osteosarcoma.
HCFC1R1 functions as a cytoplasmic scaffold protein that integrates transcriptional regulation with key pro-survival and proliferative signaling cascades. It directly interacts with host cell factor C1 (HCFC1) and pre-B-cell leukemia homeobox (PBX) transcription factors, including PBX1 and PBX2, and serves as a critical adaptor bridging HCFC1?CPBX complexes to downstream effectors. HCFC1R1 mediates activation of the PI3K/AKT and ERK/MAPK pathways through interaction with the p85 regulatory subunit of PI3K and subsequent AKT phosphorylation, while concurrently stabilizing ??-catenin to enhance Wnt/??-catenin/TCF/LEF transcriptional activity. Upstream regulators such as epidermal growth factor (EGF) and estrogen receptor signaling converge on HCFC1R1 to modulate its scaffolding function, whereas downstream targets include the oncogenic transcription factors c-Myc and Cyclin D1, as well as regulators of apoptosis (Bcl-2), invasion (MMP9), and epithelial-mesenchymal transition (Snail). In addition, HCFC1R1 interacts with HOX proteins and PBX3, implicating it in lineage-specific transcriptional networks.
In the osteosarcoma context, HCFC1R1 overexpression is associated with enhanced tumor cell proliferation, motility, and resistance to apoptosis, largely driven by constitutive PI3K/AKT/mTOR and RAS/ERK signaling. Disruption of HCFC1R1 in 143B cells abrogates these oncogenic signals, resulting in attenuated tumorigenic capacity. This knockout model therefore enables researchers to dissect the molecular contributions of HCFC1R1 to bone cancer progression, metastasis regulation, and crosstalk between the PI3K/AKT, ERK/MAPK, and Wnt/??-catenin axes. Moreover, the model provides a platform for evaluating the dependency of osteosarcoma cells on HCFC1R1-mediated transcriptional programs.
Typical research applications include Western blot and RT-qPCR-based confirmation of pathway inhibition, MTT and colony formation assays for proliferation assessment, Transwell migration and invasion assays to quantify metastatic potential, and Annexin V apoptosis assays to evaluate cell death induction. The polyclonal population is also suited for xenograft tumor growth studies to assess in vivo tumorigenicity and for transcriptomic profiling via RNA-seq to map global gene expression changes upon HCFC1R1 loss. This product is an essential tool for oncogenic signaling studies, bone cancer biology investigations, drug target validation, and tumor microenvironment research. For further details or to place an order, please contact Ascent Research.
