The HSF1 Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the HSF1 gene has been disrupted in the HCT 116 human colorectal carcinoma line. This heterogeneous cell pool provides a loss-of-function model free of clonal selection artifacts, enabling robust investigation of HSF1-mediated processes in a tumorigenic context.
The HCT 116 parental line is a microsatellite-instable (MSI-high) human male colorectal carcinoma with a KRAS G13D mutation. These tumorigenic colon epithelial cells are a well-established model for colorectal cancer studies, exhibiting constitutive activation of MAPK and PI3K/AKT pathways that drive proliferation and survival. Their defined genetic landscape and drug sensitivity profile make them ideal for dissecting oncogene-dependent stress responses.
HSF1 functions as the master transcriptional regulator of the heat shock response, becoming activated by proteotoxic insults such as heat shock, oxidative stress, hypoxia, and nutrient deprivation. Activated HSF1 trimerizes and binds heat shock elements to induce expression of molecular chaperones??HSP70 (HSPA1A), HSP90AA1, HSP27 (HSPB1)??and co-chaperones like BAG3. Its activity is tightly controlled by upstream kinases (AKT, mTOR, GSK3??) and interactions with HSP90, HSP70, and HDAC6, linking stress sensing to cell survival. Through these targets, HSF1 promotes proteostasis, inhibits apoptosis, and supports tumor cell proliferation and drug resistance.
In the HCT 116 background, oncogenic KRAS drives elevated protein synthesis and metabolic flux, imposing proteotoxic stress that likely heightens dependency on HSF1. Disruption of HSF1 in this MSI-high, KRAS-mutant context may impair stress adaptation, reduce survival under heat shock or proteasome inhibition, and sensitize cells to HSP90 inhibitors. This knockout model thus provides a powerful tool to study HSF1??s role in sustaining the malignant phenotype and to explore synthetic lethal interactions.
This polyclonal HSF1 knockout population supports diverse applications, including Western blotting for HSF1 and HSP70, RT-qPCR of target genes, cell viability/proliferation assays (MTT, colony formation), and apoptosis analysis (Annexin V). Researchers can perform drug sensitivity studies with proteasome or HSP90 inhibitors, heat shock survival assays, RNA-seq for transcriptomics, ChIP-qPCR for HSF1 promoter binding, and flow cytometry for cell cycle distribution. The model is also compatible with high-throughput screening of HSF1 inhibitors and metabolic profiling (Seahorse). For further details, please contact Ascent Research.
