This CRISPR/Cas9-edited polyclonal HSF1 knockout cell population, derived from the PaTu 8988t pancreatic ductal adenocarcinoma cell line, provides a powerful loss-of-function model to dissect HSF1-mediated transcriptional programs. Generated through CRISPR/Cas9-mediated gene disruption, this polyclonal pool harbors a genetically heterogeneous knockout of the HSF1 gene, enabling robust assessment of HSF1-dependent phenotypes without clonal artifacts.
PaTu 8988t is an epithelial cell line isolated from a liver metastasis of a human pancreatic ductal adenocarcinoma. It harbors oncogenic KRAS G12V and TP53 R282W mutations, conferring an aggressive tumorigenic phenotype and recapitulating key features of metastatic PDAC, including invasive growth and drug resistance. It is widely used to study pancreatic cancer progression and molecular mechanisms underlying metastasis.
HSF1 functions as a master transcriptional regulator of the heat shock response, activated by proteotoxic stress, oxidative stress, and signals from AKT, mTOR, p38 MAPK, and GSK3??. Upon stress, HSF1 trimerizes, binds heat shock elements (HSEs), and drives expression of molecular chaperones such as HSPA1A (HSP70), HSP90AA1, and HSPB1 (HSP27), along with co-chaperone BAG3 and anti-apoptotic BCL2L1. HSF1 interacts with HSP90, HSP70, HSBP1, and transcriptional cofactors BRG1 and p300/CBP, while SIRT1 and FOXO3a provide negative regulation. Through these interactions, HSF1 maintains proteostasis and supports oncogenic signaling, promoting cell survival, proliferation, and metastasis.
In the PaTu 8988t pancreatic cancer context, HSF1 disruption impairs the cellular stress response, sensitizing cells to proteotoxic insults and chemotherapeutics. Since HSF1 is frequently hyperactivated in PDAC and linked to therapy resistance and metastasis, this polyclonal knockout model allows dissection of HSF1-dependent malignant phenotypes, including proliferation, migration, and anchorage-independent growth, and cross-talk with the PI3K/AKT/mTOR and MAPK/ERK pathways.
Typical research applications include heat shock survival assays, Western blotting and RT-qPCR for HSF1 and downstream chaperones, ChIP-qPCR to assess HSF1 binding to HSEs, HSE-luciferase reporter assays, drug sensitivity testing, and migration/invasion assays. This product supports pancreatic cancer research, development of HSF1 inhibitors, and studies on proteotoxic stress modulation. For additional technical information or inquiry, please contact Ascent Research.
