The ACSS2 Knockout HCT 116 Polyclonal Cells product provides a genetically disrupted, heterogeneous population of human colorectal carcinoma HCT 116 cells with targeted knockout of the ACSS2 gene via CRISPR/Cas9-mediated gene disruption. This polyclonal knockout cell pool serves as a loss-of-function model for studying acetyl-CoA synthetase short-chain family member 2 (ACSS2) function without clonal selection.
The HCT 116 cell line is a well-characterized model of colorectal carcinoma, exhibiting microsatellite instability yet proficient mismatch repair. It harbors activating mutations in KRAS (G13D) and ??-catenin, driving constitutive signaling through MAPK and Wnt pathways, and is extensively employed to investigate colorectal cancer pathogenesis, drug responses, and metabolic adaptations.
ACSS2 encodes a cytoplasmic and nuclear acetyl-CoA synthetase that catalyzes the conversion of acetate to acetyl-CoA, a critical substrate for de novo lipogenesis and histone acetylation under nutrient-limited conditions. ACSS2 is transcriptionally regulated by SREBP1 and HIF-1?? during hypoxia and nutrient deprivation, and its product acetyl-CoA serves as a donor for histone acetyltransferases such as CBP/p300, linking cellular metabolism to epigenetic control. ACSS2 activity is modulated by mTORC1 signaling and AMPK phosphorylation, and it functions cooperatively with ATP citrate lyase (ACLY) and fatty acid synthase (FASN) to supply acetyl-CoA for membrane lipid synthesis, particularly in lipid-depleted tumor microenvironments. Nuclear ACSS2 is recruited by TFEB to support local acetyl-CoA production for histone acetylation at growth-promoting genes, highlighting its dual metabolic and transcriptional roles.
In HCT 116 cells, ACSS2 is particularly important for sustaining proliferation under lipid-depleted conditions by fueling acetyl-CoA pools for fatty acid and cholesterol biosynthesis, processes essential for membrane biogenesis. Moreover, loss of ACSS2 is expected to impair histone acetylation dynamics, altering gene expression programs that support colorectal tumor growth and survival. This knockout model thus enables dissection of the interplay between acetate metabolism, epigenetic regulation, and metabolic stress responses in a genetically defined colorectal cancer background.
Researchers can employ this polyclonal ACSS2 knockout pool to investigate acetate-dependent metabolic plasticity in colorectal cancer using 13C-acetate tracing coupled with LC-MS metabolomics, assess de novo lipogenesis through FASN and ACC expression by RT-qPCR, and evaluate histone acetylation changes via western blotting or ChIP-qPCR at relevant gene promoters. Functional studies may include cell proliferation assays under lipid-free culture conditions, soft agar colony formation to assess anchorage-independent growth, and xenograft tumor growth assays to evaluate the contribution of ACSS2 to tumorigenesis in vivo. For further information or customized services, please contact Ascent Research.
