Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications

HCC is one of the deadliest malignancies with a rising global occurrence and poor prognosis. Metastasis and invasion are essential processes in the HCC progression, and have a profound bearing on clinical outcome. This review explores the key signalling pathways involved in HCC metastasis and invasion, focusing on their molecular mechanisms, crosstalk, and therapeutic implications. Alongside the discussion of the Wnt/β-catenin, TGF-β, PI3K/AKT/mTOR, MAPK/ERK, HGF/c-MET, Notch and Hippo-YAP/TAZ pathways, are known to contribute to promoting aggressive HCC behaviour. Stromal interactions, extracellular matrix remodelling, hypoxia and angiogenesis as well as the tumour microenvironment are also highlighted. These pathways are subject to current therapeutic treatments in the form of tyrosine kinase inhibitors and monoclonal antibodies, and research prospective of the Wnt/β-catenin blocker, TGF-β inhibitors, etc. The variations in tumours and resistance patterns to treatment and their existing problems in treating HCC are addressed. The review evaluates new therapeutic targets offering a foundation for further research and clinical advancements in this challenging field.