Our new paper in Advanced Science

Congrats to Johnson and the team! Our paper “Chemotherapy enriched THBS2-deficient cancer stem cells drive hepatocarcinogenesis through matrix softness induced histone H3 modifications” is accepted for publication in Advanced Science.

Findings of this study show that extracellular matrix remodeling by chemotherapy 5-FU enriched THBS2-deficient CD133 cancer stem cells can provide a route of escape that leads to HCC metastasis. In brief, 5-FU enriches for CD133 expressing cells with deficient THBS2 expression. THBS2, which is a known extracellular matrix (ECM)-modifying protein, has the ability to alter MMP2/MMP9 activity and thus collagen and matrix stiffness, which leads to altered cancer and stemness properties. This local soft microenvironment then induces mechano-epigenetic changes to enhance CD133 expression and suppress THBS2 expression through histone H3 modifications at their respective promoter regions, facilitating a positive feedback loop that supports the clonogenic expansion of a subpopulation of HCC cells with high CD133 expression and low THBS2 expression.

Congrats to Steve on his Hepatology paper!

Read all about Steve’s REX1 story in the upcoming issue of Hepatology. In brief, the work describes a critical repressive function of REX1 in maintenance of HCC cells by regulating MKK6 binding and p38 MAPK signaling. REX1 deficiency induced enhancement of p38 MAPK signaling, leading to F-actin reorganization and activation of NRF2-mediated oxidative stress response, which collectively contributed to enhanced stemness and metastatic capabilites of HCC cells.

Luk ST, Ng KY, Zhou L, Tong M, Wong TL, Yu HJ, Lo CM, Man K, Guan XY, Lee TK, Ma S. Deficiency in embryonic stem cell marker REX1 activates MKK6-dependent p38 MAPK signaling to drive hepatocarcinogenesis. Hepatology 2019; accepted

Another paper in Hepatology!

Our joint publication with Dr Terence Lee’s team is accepted for publication in Hepatology. Congrats to Carmen, Carol and the team!

In brief, our work found SHP2 blockade by SHP099 in combination with sorafenib attenuated the adaptive resistance to sorafenib by impeding RTK-induced reactivation of the MEK/ERK and AKT signalling pathways. SHP099 in combination with sorafenib may represent a novel and safe therapeutic strategy against HCC.


Leung CO*, Tong M*, Chung KP, Zhou L, Che N, Tang KH, Ding J, Lau EY, Ng IO, Ma S^, Lee TK^. Overriding adaptive resistance to sorafenib via combination therapy with SHP2 blockade in hepatocellular carcinoma. Hepatology 2019; Epub ahead of print. *co-first authors ^co-corresponding authors

Our new paper in Hepatology

Congrats to Eric and the team on our latest paper published in Hepatology!

Our findings indicate that the PRMT6-ERK-PKM2 regulatory axis is an important determinant of the Warburg effect in HCC, and provide a mechanistic link among tumorigenicity, sorafenib resistance and glucose metabolism.
Wong TL, Ng KY, Tan KV, Chan LH, Zhou L, Che N, Hoo RL, Lee TK, Richard S, Lo CM, Man K, Khong PL, Ma S. CRAF methylation by PRMT6 regulates aerobic glycolysis-driven hepatocarcinogenesis via ERK-dependent PKM2 nuclear relocalization and activation. Hepatology 2019; Epub ahead of print.

Our new paper in Cell Reports!

Our work on arginine methylation via PRMT6 in mediating liver cancer stemness is published in this week’s issue of Cell Reports. Read all about it!

Chan LH*, Zhou L*, Ng KY*, Wong TL*, Lee TK, Sharma R, Loong JH, Ching YP, Yuan YF, Xie D, Lo CM, Man K, Artegiani B, Clevers H, Yan HH, Leung SY, Richard S, Guan XY, Huen MS, Ma S. PRMT6 regulates RAS/RAF binding and MEK/ERK-mediated cancer stemness activities in hepatocellular carcinoma through CRAF methylation. Cell Rep 2018; 25:690-701. (*equal contribution)

https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31498-0