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

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

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.