Highlights of This Issue

Abstract

Chen and Zhang and colleagues describe a systematic analysis of molecular correlates of metastasis using The Cancer Genome Atlas (TCGA) datasets across 11 different cancer types, with data involving mRNA, microRNA, protein, and DNA methylation. While some differential expression patterns associated with metastasis may be shared across multiple cancer types, each one also shows a metastasis signature that is distinct. When combining TCGA data with that from multiple independent profiling datasets of metastatic tumors, the resulting catalog of gene-level alterations, according to cancer type, provides a resource for future studies.Cytotoxic T lymphocytes (CTL) use the Fas-mediated apoptosis pathway as one of the two effector mechanisms to suppress tumors. Xiao et al. report here that the CD133+CD24loFaslo colon cancer cell subset exhibits decreased sensitivity to FasL-induced apoptosis in vitro and increased resistance to both tumor-specific CTL adoptive transfer and PD-1 blockade antibody immunotherapies in preclinical mouse tumor models in vivo. Furthermore, Fas expression level is positively correlated with colon cancer patient survival time. This study indicates that the CD133+CD24loFaslo colon cancer cells may, at least in part, underlie colon cancer resistance to immune checkpoint inhibitor immunotherapy.Protocadherins (PCDHs) are transmembrane proteins and members of the Cadherin superfamily that play well-established roles in cell adhesion and regulation of signaling pathways. Both oncogenic and tumor suppressive roles have been assigned to PCDHs. However, the roles of individual PCDHs in cancer and the mechanisms through which their gain-of-function and loss-of-function drive tumorigenesis in vivo remain poorly understood. The current study establishes a critical oncogenic function for PCDH7 in lung cancer using a novel transgenic mouse model. Moreover, somatic genome editing of Pcdh7 with CRISPR/Cas9 in KrasLSL-G12D; Tp53fl/fl mice support the potential therapeutic efficacy of PCDH7 inhibition for patients with lung cancer.Prostate cancer can develop resistance to anti-androgen therapy by reactiving Androgen Receptor (AR) signaling. The critical processes that lie downstream of AR and contribute to tumor growth and therapeutic resistance remain to be fully defined. Zennami and colleagues identified PDCD4, a tumor suppressive protein, as a key target of AR signaling in prostate cancer cells. AR signaling suppresses PDCD4 expression, through miR-21, leading to enhanced cell proliferation, survival, tumorigenesis, and castration resistance. These results uncover PDCD4 loss as a new molecular mechanism of castration resistance and suggest that pathways downstream of PDCD4 may be novel targets for therapy.