• Research
• Expressions Summer 2025

Decoding Cancer Progression

Collaborative study uncovers how mouth cancer spreads and escapes body’s defences

From left: Professor Richard Su, Professor Gao Zhang and Professor Jingya Pu.

A multicentre research team headed by the HKU Faculty of Dentistry has unlocked some of the secrets of how oral squamous cell carcinoma (OSCC), a common and aggressive form of mouth cancer, progresses to advanced-stage disease. The team’s analysis reveals key molecules and pathways that enable the cancer to spread (metastasise) and evade the body’s immune defences, paving the way for developing more precise and effective treatments.

Professor Gao Zhang (Associate Professor in Applied Oral Sciences and Community Dental Care) and Professor Richard Su (Clinical Professor in Oral and Maxillofacial Surgery) from the HKU Faculty of Dentistry led the team, which also comprised the Faculty’s Professor Jing-ya Pu and PhD candidates Yu Liu and Jie Zhong; Professor Ui-soon Khoo from the HKU Li Ka Shing Faculty of Medicine; and Dr Zhenyu Yang from the West China Hospital of Sichuan University. The study was published in March 2025 in Clinical and Translational Medicine (https://doi.org/10.1002/ctm2.70261).

Using state-of-the-art “multi-omics” techniques that examine genes, proteins, and other biological signals all at once, the researchers compared tissue samples from 46 OSCC patients: 10 whose cancer had spread beyond the mouth and 36 whose cancer had not. Their aim was to understand how OSCC spreads to nearby lymph nodes—part of the body’s immune system—but manages to avoid being detected or stopped.

Schematic summary of two patient cohorts.
(Adapted from “Proteogenomic characterisation of primary oral cancer unveils extracellular matrix remodelling and immunosuppressive microenvironment linked to lymph node metastasis”, by Gao Zhang et al., 2025, Clinical and Translational Medicine, Volume 15, Issue 3. https://doi.org/10.1002/ctm2.70261)

Compared with cancers that had not spread, those that had already spread showed faster cell growth, owing to genetic changes that stimulated cell replication. They also showed an increased level of the protein periostin (POSTN), which was linked to cancer invasion of lymph nodes, immune suppression, and remodelling of the surrounding tissue (extracellular matrix). These changes were accompanied by reduced activity of vascular cell adhesion molecule 1 (VCAM1) and increased activation of the transforming growth factor beta (TGF-β) signalling pathway. Additionally, neighbouring supportive cells known as cancer-associated fibroblasts produced TGF-β, which, in turn, facilitated cancer invasion of lymph nodes and immune suppression.

“Our results provide insights into how OSCC metastasises, bypasses immune responses, and resists conventional therapies,” said Professor Gao Zhang. “The major roles of POSTN and TGF-β in cancer spread and immune suppression indicate they are promising targets for new therapeutic strategies for stopping or slowing the spread of OSCC.”

Professor Richard Su added: “Our study lays a robust foundation for future drug development. Disrupting the interplay between cancer-associated fibroblasts and TGF-β could lead to treatments that halt cancer progression in its tracks.”

Furthermore, inhibiting extracellular matrix remodelling or TGF-β signalling might reduce immune evasion and cancer invasion, thereby improving the effectiveness of current treatments, such as immunotherapy. The team plans to explore these possibilities in the future, aiming to improve survival rates for OSCC patients.