Highlights of This Issue

Abstract

EGFR and EGFRvIII can be detected in tumor nuclei, in which nuclear EGFR regulates gene expression. It remains unknown if the nuclear EGFR pathway is valid in glioblastoma (GBM) and whether nuclear EGFRvIII plays a significant role in any cancer type. Lo and colleagues showed both receptors to undergo nuclear translocalization in GBM. Via gene expressing profiling of GBM cells with wild-type EGFR and genetically modified EGFR, COX-2 was identified as one of the novel nuclear EGFR-targeted genes. Nuclear EGFR/EGFRvIII cooperates with STAT3 to upregulate COX-2 expression, thus linking nuclear EGFR-STAT3 and nuclear EGFRvIII-STAT3 signaling axes to COX-2-mediated pro-inflammatory pathway.Abnormal expression of myeloid zinc finger 1 (MZF1) and Axl leads to cancer progression. However, the potential role of MZF1 in regulating Axl expression and metastasis is not clear. To explore MZF1's role in Axl regulation and metastasis, Mudduluru and coworkers performed in vitro and in vivo chicken– embryo–metastasis (CAM) assays either with MZF1-overexpression/sh-Axl knockdown or in combination of both. In vitro results showed that MZF1-significantly induces Axl expression and MZF1-induced migration and invasion is at least in part mediated through Axl. CAM assay showed that MZF1 significantly induces tumor formation and liver metastasis, furthermore, MZF1 expression positively correlated with Axl expression in resected colorectal cancer tissues.Elevated expression of antiapoptotic Bcl-2 not only enhances carcinoma cell survival but also increases malignant behavior leading to increased invasion and dissemination. Ectopic Bcl-2 expression in head and neck squamous cell carcinoma (HNSCC) cells promoted tumor growth and pulmonary metastasis, initiated an EMT phenotype with induction of N-cadherin expression, stimulated cell locomotion and invasion, and induced MMP-9 production through the MAPK/FGFR signaling–dependent pathway. These findings provide a basis for further characterization of the molecular mechanisms of EMT-mediated invasion that cooperate with Bcl-2 family member regulation of anti-apoptotic functions in the development of highly metastatic cell variants in HNSCC.c-Jun NH2-terminus kinase (JNK) is known to mediate the cytotoxic effect of anticancer therapies. Paradoxically, elevated JNK activity is associated with poor prognosis in human cancers. We found that hyperactive JNK did not cause apoptosis in breast cancer cells, but induced a phenotype associated with epithelial-mesenchymal transition (EMT) and enhanced ERK activation by increasing IRS-2, which upregulated the AP-1 transcription factor. Modulation of ERK by hyperactive JNK also attenuated paclitaxel-induced apoptosis. Our findings identify a novel mechanism of cross-talk between JNK and ERK signaling and might provide insight into the recently reported link between chemoresistance and EMT.