From Left to Right: Professor Yuxiong Su, Professor Gao Zhang and Professor Jingya Pu.
A collaborative research team from The University of Hong Kong (HKU) and West China Hospital of Sichuan University has made a breakthrough in understanding the spread of oral squamous cell carcinoma (OSCC), a prevalent and aggressive form of mouth cancer. Their findings, published in Clinical and Translational Medicine, reveal critical molecular changes that drive metastasis to lymph nodes and suppress immune responses, offering promising avenues for new treatment approaches.
The study was led by Professor Gao Zhang, with Professor Yu-Xiong Su as co-corresponding author, both of whom are from the HKU Faculty of Dentistry. The research team also includes Professor Jing-Ya Pu, PhD students Yu Liu and Jie Zhong from the same faculty, Professor Ui-Soon Khoo from the Li Ka Shing Faculty of Medicine, and Dr Zhen-Yu Yang from the West China Hospital of Sichuan University.
The study analysed tissue samples from 46 patients using cutting-edge multi-omics techniques—integrating genomic, transcriptomic, and proteomic data. The research pinpointed key pathways that fuel tumor progression and immune evasion, shedding light on why OSCC often becomes resistant to conventional therapies.
Decoding the Spread of Oral Cancer
The study revealed distinct differences in tumors that had metastasised to lymph nodes (pLN+ OSCC) compared to those that had not. These aggressive tumors displayed heightened growth and invasiveness, driven by genetic alterations linked to cell proliferation and extracellular matrix (ECM) remodeling—a process that enables cancer to spread. Additionally, these tumors suppressed immune responses by downregulating immune-supportive molecules like VCAM1 and activating TGF-β signaling, a pathway known to promote tumor growth and shield cancer cells from immune detection.
A standout discovery was the role of the protein POSTN, which reorganises the tumor's structural support and correlates with worse patient outcomes. High POSTN levels were linked to increased metastasis. The team also identified cancer-associated fibroblasts (CAFs)—supportive cells within the tumor—as key players in this process. CAFs amplify TGF-β signaling, enhancing the tumor's ability to invade surrounding tissues and evade the immune system.
"These insights transform our understanding of how OSCC metastasises and resists immune defenses," said Professor Gao Zhang, lead contact and co-corresponding author. "By spotlighting POSTN and TGF-β as critical drivers, we've identified promising targets for therapies to halt or prevent cancer spread."
New Hope for Treatment Innovation
The findings pave the way for novel therapeutic strategies. Targeting ECM remodeling or TGF-β signaling could bolster existing treatments, such as immunotherapy, by countering immune suppression and slowing metastasis. The HKU team aims to inspire further research and clinical trials to explore these targets, with the ultimate goal of improving survival rates for OSCC patients.
"This study lays a robust foundation for future drug development," said Professor Su. "Disrupting the interplay between CAFs and TGF-β could lead to treatments that stop tumor progression in its tracks."
Link to the article: https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70261
