Department of Pathology

Research Area

Cancer Metastasis and Tumor Microenvironment in Liver Cancer

Yam Laboratory Website: www.jyamlab.com

Research Description

Hepatocellular carcinoma (HCC) is a primary malignancy of liver and develops preponderantly in individuals with underlying chronic liver disease. HCC is an aggressive tumor with local invasion and extrahepatic metastasis as signatures in the advanced stage. Metastasis to specific organs is not a random process but results from the interplay between intrinsic properties of cancer cells and microenvironment of the distant organ. Extracellular vesicle (EV) shedding from tumor cells has emerged as an important channel for cell-cell communication in influencing the local tumor microenvironment and facilitating pre-metastatic niche formation in distant organ sites. They contain distinct components which depend on the cell type from which they are released and can subsequently be transferred to the recipient cells. EV content is regarded as a fingerprint of the releasing cells; it provides insightful information about the origin and functions of releasing cells. Circulating EV of cancer patients may therefore serve as promising biomarker for early detection and prognosis. We are interested to understand the molecular basis of EV-driven HCC metastasis by dissecting the functional role and signaling cascades of EV content. In clinical perspective, our work aims to identify promising EV content for the early diagnosis and novel therapeutic interventions for cancer patients. Using multidisciplinary approaches, our team endeavored to understand the mechanistic basis of HCC metastasis with translational impact leading to improved health, well-being and quality of life for cancer patients.

Research Interests

Functional role of tumor-derived extracellular vesicles in cancer metastasis
Role of extracellular vesicles in the formation of pre-metastatic niche
Signaling pathways underlying liver cancer metastasis driven by tumor-derived extracellular vesicles
Application of extracellular vesicles as a therapeutic delivery vehicle

Awards

Faculty Outstanding Research Output Award 2022
Outstanding Young Researcher Award (2008-2009), The University of Hong Kong

Research Grants

Research Grants Council - General Research Fund (2022, 2021, 2020, 2019, 2018, 2016, 2015, 2014, 2013, 2010, 2007, 2006)
Food and Health Bureau - Health and Medical Research Fund (2022, 2018, 2014, 2013)
ITC - Innovative and Technology Support Programme Seed Projects (2021)
ITC - Research Talent Hub (2021)
Shenzhen Science and Technology Innovation Commission - Shenzhen-Hong Kong-Macau Technology Research Programme (Type C) (2022)
National Natural Science Foundation of China - General Program (2020, 2018)
Society of Hong Kong Scholars and China National Postdoctoral Council - Hong Kong Scholars Program (2022, 2020)
State Key Laboratory of Liver Research, The University of Hong Kong

Selected Publications

#Co-first author; *Corresponding author

Tey SK, Yam JWP*. The importance of activated TMPRSS2 in proviral role of extracellular vesicles in SARS-CoV-2 infection. Journal of Extracellular Vesicles 2023, 11(12):e12296. [IF: 17.337]
Xiao XJ, Yeung CLS, Yam JWP, Mao XW*. An update in the role of complement in hepatocellular carcinoma. Frontiers in Immunology 2022, 13:1007382. [IF: 8.786]
Chen Z, Yam JWP*. Recent advances in liquid biopsy in cancers: Diagnosis, disease state and treatment response monitoring. Clinical and Translational Discovery 2022, 2:e111
Tey SK, Lam H, Wong SWK, Zhao H, To KKW*, Yam JWP*. ACE2-enriched extracellular vesicles enhance infectivity of live SARS-CoV-2 virus in an endocytosis-dependent manner. Journal of Extracellular Vesicles 2022 11(5):e12231. [IF: 17.337]
Mei P, Tey SK, Wong SWK, Ng TH, Mao XW, Yeung CLS, Xu Y, Yu L, Huang Q, Cao P, Yam JWP*, Gao Y*. Actin Related Protein 2/3 Complex Subunit 2-enriched extracellular vesicles drive liver cancer metastasis. Hepatology International 2022, 16(3):603-613. [IF: 9.052]
Tey SK, Wong SWK, Yeung CLS, Li JYK, Mao XW, Chung CYS, Yam JWP*. Liver cancer cells with nuclear MET overexpression release translation regulatory protein-enriched extracellular vesicles exhibit metastasis promoting activity. Journal of Extracellular Biology 2022, 1:e39.
Yeung CLS, Yam JWP*. Therapy-induced modulation of extracellular vesicles in hepatocellular carcinoma. Seminars in Cancer Biology 2022, 86(Pt 3):1088-1101. [IF: 17.012]
Tey SK#, Wong SWK#, Chan JYT, Mao XW, Ng TH, Yeung CLS, Leung Z, Fung HL, Tang AHN, Wong DKH, Mak LY, Yuen MF, Sin CF, Ng IOL, Ma SKY, Lee TKW, Cao PH, Zhong K, Gao Y, Yun JP, Yam JWP*. Patient pIgR-enriched extracellular vesicles drive cancer stemness, tumorigenesis and metastasis in hepatocellular carcinoma. Journal of Hepatology 2022, 76(4): 883-895. [IF: 30.083] - Featured by editorial: Journal of Hepatology 2022, 76(4): 768-770.
Liu BHM, Tey SK, Mao XW, Ma APY, Yeung CLS, Wong SWK, Ng TH, Xu Y, Yao Y, Fung EYM, Tan KV, Khong PL, Ho DWH, Ng IOL, Tang AHN, Cai SH, Yun JP, Yam JWP*. TPI1-reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis. Journal of Extracellular Vesicles 2021, 10:e12135. [IF: 17.337]
Ma APY, Yeung CLS, Tey SK, Mao XW, Wong SWK, Hg, TH, Ko FCF, Kwong EML, Tang AHN, Ng IOL, Cai SH, Yun JP, Yam JWP*. Suppression of ACADM-mediated fatty acid oxidation promotes hepatocellular carcinoma via aberrant Cav1/SREBP-1 signaling. Cancer Research 2021, 81:3679-3692. [IF: 13.312]
Mao XW#, Zhou LY#, Tey SK, Ma APY, Yeung CLS, Ng TH, Wong SWK, Liu BHM, Fung EYM, Patz EF Jr, Cao PH, Gao Y, Yam JWP*. Tumor extracellular vesicle-derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement-dependent cytotoxicity of tumor cells. Journal of Extracellular Vesicles 2020, 10(1):e12031. [IF: 17.337]
Mao XW#, Tey SK#, Yeung CLS, Kwong EML, Fung YMF, Chung CYS, Mak LY, Wong DKH, Yuen MF, Ho JCM, Pang H, Wong MP, Leung CON, Lee TKW, Ma V, Cho WCS, Cao PH, Xu X, Gao Y, Yam JWP*. Nidogen 1-enriched extracellular vesicles facilitate extrahepatic metastasis of liver cancer by activating pulmonary fibroblasts to secrete tumor necrosis factor receptor 1. Advanced Science 2020, 7:2002157. [IF: 17.337]
Leung Z, Ko FCF, Tey SK, Kwong EML, Mao XW, Liu BMH, Ma APY, Fung YMF, Che CM, Wong DKH, Lai CL, Ng IOL, Yam JWP*. Galectin-1 promotes hepatocellular carcinoma and the combined therapeutic effect of OTX008 galectin-1 inhibitor and sorafenib in tumor cells. Journal of Experimental & Clinical Cancer Research 2019, 38:423. [IF: 12.658]
Mao XW, Tey SK, Ko FCF, Kwong EML, Y Gao, Ng IOL, ST Cheung, XY Guan, Yam JWP*. C-terminal truncated HBx protein activates caveolin-1/LRP6/beta-catenin/FRMD5 axis in promoting hepatocarcinogenesis. Cancer Letters 2019, 444:60-69. [IF: 9.756]
Tey SK, Tse EYT, Mao XW, Ko ECF, AST Wong, Lo RCL, Ng IOL, Yam JWP*. Nuclear Met promotes hepatocellular carcinoma tumorigenesis and metastasis by upregulation of TAK1 and activation of NF-κB pathway. Cancer Letters 2017, 411:150-161. [IF: 9.756]
Mao XW, Wong SYS, Tse EYT, Ko FCF, Tey SK, Yeung YS, Man K, Lo RCL, Ng IOL, Yam JWP*. Mechanisms through which hypoxia-induced caveolin-1 drives tumorigenesis and metastasis in hepatocellular carcinoma. Cancer Research 2016, 76:7242-7253. [IF: 13.312]
Ko FCF, Chan LK, Sze KMF, Yeung YS, Tse EYT, Lu P, Yu MH, Ng IOL, Yam JWP*. Induced dimerization of DLC1 by PKA contributes to the tumorigenesis and metastasis inhibitory activities of DLC1 via enhanced RhoGAP activity. Nature Communications 2013, 4:1618. [IF: 17.694]
Tse EYT, Ko FCF, Tung EKK, Chan LK, Lee TKW, Ngan ESW, Man K, Wong AST, Ng IOL, Yam JWP*. Caveolin-1 is overexpressed and associated with hepatocellular carcinoma tumorigenesis and metastasis. Journal of Pathology 2021, 226:645-653. [IF: 9.883]
Ko FCF, Chan LK, Tung EKK, Lowe SW, Ng IOL, Yam JWP*. Akt phosphorylation of Deleted in Liver Cancer 1 deregulates its suppression of liver cancer tumorigenesis and metastasis. Gastroenterology 2010, 139(4):1397-1407. [IF: 33.883] - Featured by editorial: Gastroenterology 2010, 139(4): 1093-1096
Yam JWP, Ko FCF, Chan CY, Yau TO, Tung EKK, Leung THY, Jin DY, Ng IOL*. Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma. Hepatology 2006, 44:881-890. [IF: 17.298]
Yam JWP, Ko FCF, Chan CY, Jin DY, Ng IOL*. Interaction of DLC1-tensin2 complex with caveolin-1 and implications in tumor suppression. Cancer Research 2006, 66:8367-8372. [IF: 13.312]
Wong CM#, Yam JWP#, Ching YP, Yau TO, Leung HY, Jin DY, Ng IOL*. Rho GTPase activating protein DLC1 (deleted in liver cancer 1) suppresses cell proliferation and invasion in hepatocellular carcinoma. Cancer Research 2005, 65:8861-8868. [IF: 13.312]
Yam JWP, Jin DY, So CW, Chan LC*. Identification and characterization of EBP, a novel EEN binding protein that inhibits ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein. Blood 2004, 103:1445-1453. [IF: 25.476]
Yam JWP, Chan KW, Hsiao WLW*. Transcriptional regulation of rat frizzled related protein gene promoter by CREB. Oncogene 2003, 22:3901-3910. [IF: 8.756]
Yam JWP, Chan KW, Hsiao WLW*. Suppression of the tumorigenicity of mutant p53-transformed rat embryo fibroblasts through expression of a newly cloned rat nonmuscle myosin heavy chain-B. Oncogene 2001, 20:58-68. [IF: 8.756]

Team Members

Mao Xiaowen (Research Assistant Professor)
Tony Ng (Postdoctoral Fellow)
Xu Yi (Postdoctoral Fellow)
Zhang Xiaoxin (Postdoctoral Fellow)
Yao Yue (Research Assistant)
Helena Fung (Research Assistant)
Natalie Chan (Research Assistant)
Cherlie Yeung (PhD Student)
Samuel Wong (PhD Student)
Chen Zhixian (PhD Student)
Chen Li (PhD Student)
Charlotte Lai (PhD Student)
Kelly Lee (MPhil Student)
Nicholas Lau (BBMS FYP Student)
Yu Liang (Student Research Assistant)
Xue Tingmao (Student Research Assistant)

Achievements of Team Members

Nicholas LAU, BBMS FYP student (2022 - 2023)

Undergraduate Research Fellowship Programme 2022-2023 - Research Internship Award

Li CHEN, PhD student (2022 - 2025)

HKUMed’s Doctoral Entrance Scholarship for Medical Research Excellence

Xu Yi, PDF (2021 - 2023)

Best Oral Presentation Award, Hong Kong Scholar Annual Symposium, 2022

Zhixian Chen, PhD student (2021 - 2025)

University Postgraduate Fellowship

Samuel Wong, PhD student (2021 - 2025)

Best Poster Presentation Award, RPG Symposium, LKS Faculty of Medicine, 2022
Best Oral Presentation Award, SKLLR Internal Meeting, 2022
Most Innovative Award, Departmental RPG Retreat, Department of Pathology, 2022
Foreign Investigator Award, The Liver Week, 2021

Cherlie Yeung, PhD student (2020 - 2024)

Best Poster Award, Annual Scientific Meeting of Hong Kong Society of Flow Cytometry, 2022
Wong Ching Yee Medical Postgraduate Scholarship 2021/2022
Best Poster Presentation Award, RPG Symposium, LKS Faculty of Medicine, 2021
Best Presentation Award, Departmental RPG Retreat, Department of Pathology, 2021
Poster Presentation Award, Hong Kong Inter-University Symposium in Biomedical Sciences, 2021
Foreign Investigator Award, The Liver Week, 2021
Best Poster Presentation Prize, RPG Symposium, LKS Faculty of Medicine, 2020
SKLLR RPG Scholarship Supporting Scheme, 2020

Angel Ma, PhD student (2016 - 2020)

Best Poster Presentation Award, RPG Symposium, Faculty of Medicine, 2018
SKLLR RPG Scholarship Supporting Scheme, 2016
Blue Ocean Basic Medical Research Fund, 2016

Bonnie Liu, PhD student (2016 - 2020)

University Postgraduate Fellowship, 2016

Sze Keong Tey, PDF (2015 - 2021), PhD student (2011 - 2015)

Travel Award, The Liver Week, 2017
Travel Award, The Liver Week, 2016
Graduate Student Travel Scholarship, Tigris Educational Fund, 2015
Best Presentation Award, RPG Symposium, Faculty of Medicine, 2014
Best Presentation Award, RPG Retreat, Department of Pathology, 2013

Edith Tse, PhD student (2008 - 2011)

Best Presentation Award, 8th RPG Retreat, Department of Pathology, 2010
Best Presentation Award, 9th RPG Retreat, Department of Pathology, 2010
YS and Christabel Lung Postgraduate Scholarship, 2008/2009
Young Investigator Award, Hong Kong International Cancer Congress, 2008

Lo Kong Chan, PhD student (2004 - 2008)

Best Presentation Award, RPG Retreat, Department of Pathology, 2008
Outstanding Oral Presentation Award (Cancer session), RPG Symposium, Faculty of Medicine, 2007