Fighting cancer by molecular mechanism and cell migration
Professor Michael Yang Mengsu, CityU Vice-President (Research and Technology) (3rd from right), led the research team. (From left: Zhou Li, CityU Research Assistant and PhD student at Chongqing Medical University, Kelvin Ng Kaki and Eileen Yang Zihan, CityU PhD students, Professor Yang, Wang Zesheng and Si Tongxu, CityU PhD students.)
A novel protein, Lysyl hydroxylase 1 (LH1) has been discovered to be a key factor in promoting cancer cell migration and metastasis in liver cancer (hepatocellular carcinoma, HCC) and pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC), according to CityU researchers.
The team also found that a high LH1 level is associated with poor prognosis (the development of disease and long-term survival) of HCC and PDAC patients. The team expects the research findings to provide a new potential treatment target for cancer therapy. The team expects the research findings to provide a new potential treatment target for cancer therapy.
Cancer metastasis is a major cause of cancer-related death, and the migration of cancer cells through increasingly stiff solid tumours is a common feature of HCC and PDAC metastasis, but the mobility of cells in the tumour microenvironment remains poorly understood.
“We aim to study the molecular mechanism of cancer cell migration in the confined microenvironment and to identify novel genes and proteins related to the process,” said Professor Michael Yang Mengsu, Vice-President (Research and Technology) and Yeung Kin Man Chair Professor of Biomedical Sciences at CityU, who led a multi-institution team to conduct the research.
The research team discovered that LH1 enhances the migration capability, including speed and invasion capacity of HCC and PDAC cells in confined space through binding and stabilising Septin2 (SEPT2), a protein that plays an essential role to ready the cells for the high mechanical demands of migration, thus promoting the metastasis of HCC and PDAC cells.
They also discovered that high LH1 expression is correlated with poor prognosis for both HCC and PDAC patients.
LH1 was strongly expressed in HCC tumour embolus. (Credit: © Yang, Z. et al. https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-023-01727-9)
“The main challenge in this research is recreating the complex cancer microenvironment, but the team successfully developed a series of multidimensional 2D and 3D in vitro and in vivo models to comprehensively study the cancer cell migration process in confined space,” explained Professor Yang.
“The findings are expected to provide a potential new target for cancer diagnosis and drug development.”