PIGK regulates lipophagy in colorectal cancer through ABHD5

BACKGROUND: Colorectal Cancer (CRC) is a prevalent malignant tumor with a high incidence and mortality rate worldwide. Despite the availability of various treatment options, CRC remains a significant health challenge due to its complexity and heterogeneity. The objective of this study is to investigate the role of PIGK in CRC and to elucidate the underlying mechanisms that contribute to its impact on the disease. RESULTS: Our analysis of the TCGA database revealed that PIGK expression is significantly elevated in CRC tissues compared to normal tissues, with higher expression levels correlating with improved patient prognosis. In vitro experiments demonstrated that PIGK can suppress the proliferation of CRC cells by promoting autophagy. Further mechanistic exploration showed that PIGK upregulates the expression of ABHD5, influencing lipophagy. We also identified the pivotal role of the PIGK-ABHD5-PPARα signaling pathway in the regulation of lipophagy. Tumorigenesis experiments in nude mice confirmed PIGK's inhibitory effect on tumor growth and its role in modulating lipophagy through ABHD5. CONCLUSIONS: In summary, our findings not only highlight PIGK as a novel molecular target in CRC but also suggest that targeting the PIGK-ABHD5-PPARα signaling axis could offer a promising therapeutic strategy. By influencing lipophagy, PIGK presents a potential avenue for improving CRC treatment outcomes, which could have significant implications for patient management and the development of new treatment protocols.