Highlights of This Issue

DOI: Published September 2014

Determinants of In Vivo ABT-263 Response

Suryani et al. Page 4520

Manipulation of the apoptosis pathway is an appealing strategy for cancer treatment using BH3 mimetics such as ABT-263, although predictive biomarkers are required to identify patients who may benefit from their use. To investigate this problem, Suryani and colleagues studied the in vivo efficacy of ABT-263 against 31 pediatric acute lymphoblastic leukemia xenografts. High MCL1 expression and function correlated with in vivo ABT-263 resistance, and in vitro assays predicted in vivo ABT-263 responses. These approaches could be included in the design of prospective clinical trials to determine if they can identify patients who may respond to treatment with this class of therapeutic agents.

Gastric Cancer Methylome and Metastasis Biomarkers

Liu et al. Page 4598

Gastric carcinoma (GC) is the second leading cause of cancer deaths in the world, with many deaths occurring in East Asia. To identify DNA methylation biomarkers for prediction of GC metastasis, scientists, and oncologists from China, the United States, Japan, and Korea have profiled differential methylation patterns in GCs and perform an in-depth characterization of methylation changes in 73 candidate genes. The authors have established a methylation biomarker-set composed of three genes GFRA1, SRF, and ZNF382 that could be used to synergistically predict GC metastasis and patients' overall survival from multiple patient cohorts in China, Japan, and Korea.

Tumorigenic Role of TAZ in NSCLC

Noguchi et al. Page 4660

TAZ, the core component of Hippo signaling pathway, attracts increasing attention as a critical player in tumorigenesis. Using an integrated translational approach, the authors explored the role of TAZ in non-small cell lung cancer (NSCLC). Noguchi and colleagues showed that higher TAZ expression was associated with shorter patient survival, and TAZ promoted lung cancer cell proliferation in vitro and tumor development in vivo. Moreover, TAZ regulated the expression of ErbB ligands and the EGFR signaling pathway was activated in NSCLC tissues with high TAZ expression. This study offers potential therapeutic strategies, either directly against TAZ or indirectly via EGFR pathway.

GSK-3β-regulated N-Acetyltransferase 10 in Colorectal Cancer

Zhang et al. Page 4717

Activation of Wnt-signaling is a common event in colorectal carcinoma (CRC), but its role in CRC metastasis is still under extensive study. In the present study, Zhang and colleagues revealed subcellular redistribution of NAT10 (N-acetyltransferase 10) in CRCs, which correlated well with nuclear translocation of β-catenin and reflected invasive potential of CRC. They demonstrated that inhibition of GSK-3β induced NAT10 redistribution through increasing its stability and nuclear export, which consequently enhanced cytoskeletal remodeling and promoted migration, invasion, and metastasis of cancer cells. These findings suggest NAT10 could be a useful prognostic marker and potential therapeutic target in CRC.