Molecular Mechanisms of Cancer Progression and Metastasis

Cancer progression and metastasis arise from a complex interplay of genetic alterations, aberrant signalling pathways, and dynamic interactions with the surrounding microenvironment. Key oncogenic drivers such as Ras/MAPK and PI3K/AKT pathways converge on transcription factors like Snail, Twist and ZEB to induce epithelial–mesenchymal transition (EMT), enabling epithelial cells to adopt migratory and invasive phenotypes. Concomitantly, cancer cells reprogramme energy metabolism towards aerobic glycolysis and glutamine addiction, while hypoxia stabilises HIF-1α to drive angiogenesis, enhancing nutrient and oxygen supply. Within the primary tumour niche, stromal cells, immune subsets and extracellular matrix components create a supportive milieu that fosters local invasion, intravasation into the vasculature, survival in circulation and eventual colonisation of distant organs. Cancer stem cell (CSC) subpopulations, characterised by self-renewal capacity and plasticity, further underpin metastatic colonisation and therapy resistance. Epigenetic regulators and post-translational modifiers such as ubiquitin ligases fine-tune these processes, offering numerous potential biomarkers and therapeutic targets. A detailed molecular understanding of each step in the metastatic cascade is essential for the design of interventions that can intercept dissemination, prevent relapse and improve patient survival worldwide.

Research from Nature Portfolio

Recent studies have elucidated how loss of the Ras GTPase-activating protein DAB2IP unleashes NF-κB-driven EMT and enhances cancer stem cell traits in colorectal carcinoma. Genetic ablation of DAB2IP in murine colonic epithelium produces hyperplastic lesions with mesenchymal characteristics and heightened NF-κB activity. In patient samples, reduced DAB2IP expression correlates inversely with tumour differentiation, metastasis and overall survival, highlighting its prognostic value. Mechanistically, DAB2IP restrains NF-κB signalling to maintain epithelial identity and suppress stem-like features, thereby limiting both local invasion and distant colonisation. Restoring DAB2IP or targeting downstream effectors of its pathway offers a promising route to inhibit metastatic progression.

Molecular Mechanisms of Cancer Progression and Metastasis publication trend

The graph below shows the total number of articles in molecular mechanisms of cancer progression and metastasis across all publications each year (not limited to Nature Index journals).

Technical terms

Epithelial–mesenchymal transition (EMT): The process by which epithelial cells lose polarity and adhesion to acquire migratory mesenchymal properties.

Cancer stem cell (CSC): A subpopulation of tumour cells with self-renewal capacity and differentiation potential that contributes to metastasis and relapse.

Ubiquitination: Post-translational modification tagging proteins for degradation by the proteasome.

Ras GTPase-activating protein (RasGAP): A regulator that inactivates Ras signalling by accelerating GTP hydrolysis.

Hypoxia-inducible factor-1α (HIF-1α): A transcription factor stabilised under low oxygen that promotes angiogenesis and metabolic reprogramming.

References

1. An update on the tumor-suppressive functions of the RasGAP protein DAB2IP with focus on therapeutic implications. Cell Death & Differentiation (2024).
2. Lipophagy-related gene RAB7A is involved in immune regulation and malignant progression in hepatocellular carcinoma. Computers in Biology and Medicine (2023).
3. DAB2IP inhibits glucose uptake by modulating HIF-1α ubiquitination under hypoxia in breast cancer. Oncogenesis (2024).