ACSL5 (Acyl-CoA Synthetase Long Chain Family Member 5)

Notably, JAB1 inhibition reverses chemotherapy resistance associated with CUL4B overexpression. These findings underscore the pivotal role of JAB1 in regulating breast cancer progression and indicate that JAB1 inhibitors could serve as promising therapeutics for patients with elevated CUL4B expression.

Nonetheless, these metabolic increases also generate reactive oxygen species (ROS), inducing DNA damage and significantly enhancing colorectal cancer cell sensitivity to oxaliplatin. The latter provides an explanation as to why colorectal tumors with high ACSL5 expression display preferentially improved patient outcomes from chemotherapy. Collectively, the findings reveal a new pathway for non-genetic chemotherapy resistance mechanisms, deepen the understanding of metabolic reprogramming in tumor cells, and offer potential therapeutic targets for future treatment strategies.

The present review seeks to fill this gap by summarizing recent advances in understanding the roles of the ACSL family across diverse diseases, with a focus on emerging therapeutic strategies that target these enzymes. This work provides critical insights that may inform future preclinical and clinical investigations of the ACSL family.

These results indicate that OCIAD2 is a potential prognostic biomarker and therapeutic target for PC patients.

Finally, SOX2 expression correlates negatively with ACSL5 and positively with histone acetylation in clinical esophageal squamous tumors. Altogether, our study uncovers a role of SOX2 in reprogramming lipid metabolism and driving histone hyperacetylation and super-enhancer function, providing mechanistic insights of SOX2 acting as a potent oncodriver.

Lastly, single-cell RNA-sequencing revealed elevated ACSL4 expression in immune cells in a murine MASH-HCC model, suggesting a role of ACSL4 in shaping the tumor immune microenvironment. Overall, this report offers new insights into lipid metabolic landscape and ferroptosis sensitivity for novel MASH-HCC treatments.

These results provide valuable insights into potential biomarkers and therapeutic targets for BLCA treatment. The CHMP6 protein promotes BLCA cell survival and invasive migration through modulation of the cell cycle.

In summary, our study revealed that ACSL5-mediated lipid oxidation increases the acetyl-CoA content, promotes cellular senescence, and inhibits the proliferation of BC. The activation of ACSL5-mediated lipid oxidation to regulate cellular senescence may provide an innovative direction for BC therapy.

The GFSscore may offer patients personalized therapy by identifying new therapeutic targets for tumors. By understanding the relationship between cancer metabolism and the immune microenvironment, we can better tailor treatments to individual patients.

The inhibition of ACSL5 activity or TAG biosynthesis suppresses AKT phosphorylation and KSHV lytic reactivation, restoring the phenotype of PINLYP deficiency. This finding underscores the pivotal role of PINLYP in remodeling phospholipid metabolism and promoting viral latency, which sheds new light on how phospholipid metabolism is regulated by herpesvirus and provides a potential target for controlling chronic herpesvirus infection.

In summary, Hp II acts as a dual-pathway inducer targeting both cholesterol-driven CA and KIF11-mediated centrosome separation to trigger ferroptosis. These findings position Hp II-KIF11 as a metabolic-mitotic ferroptosis regulator, connecting cholesterol metabolism, centrosome dynamics, and oxidative cell death.

ScRNA-seq revealed the predominant expression of these genes in myeloid cells, with differential expression validated using qRT-PCR in thyroid tumour and normal tissues. This study integrates bulk and single-cell RNA sequencing data to identify IRFGs and construct a robust prognostic model, offering new therapeutic targets and improving prognostic evaluation for thyroid cancer patients.