Celecoxib appears to induce apoptosis in human NSCLC through the extrinsic death receptor pathway.

No abstract

Strigolactones (SLs), a class of the most recently identified terpenoid phytohormones, play essential roles in plant development, specifically in suppressing shoot branching. MAX2, a subunit of an SCF E3 ligase and a positive regulator that inhibits shoot branching, is likely a key SL signaling component. Here, we provide genetic and biochemical evidence to demonstrate that BES1 interacts with MAX2 and acts as its substrate to regulate SL-responsive gene expression. Additional AtD14, a putative receptor of SLs, can promote BES1 degradation. Knockdown of BES1 and its homologs dramatically suppressed the branching phenotype of max2-1 mutant. These results portray an SL signaling cascade from the putative receptor to downstream transcription factors. In addition, we demonstrate that the SL and brassinosteroid (BR) signaling pathways distinctly regulate the same transcription factor, BES1, to control specific developmental processes.

No abstract

Brassinosteroids (BRs) are plant-specific steroid hormones that control plant growth and development. Recent studies have identified key components of the BR signaling pathway in and in rice (); however, the mechanism of BR signaling in rice, especially downstream of GSK3/SHAGGY-like kinase (GSK2), remains unclear. Here, we identified a BR-insensitive rice mutant, (), and cloned the corresponding gene. was identical to the previously reported (), which was cloned from another allele. encodes a transcription factor with an APETALA2 DNA binding domain. Genetic analysis indicated that RLA1/SMOS1 functions as a positive regulator in the BR signaling pathway and is required for the function of BRASSINAZOLE-RESISTANT1 (OsBZR1). In addition, RLA1/SMOS1 can interact with OsBZR1 to enhance its transcriptional activity. GSK2 can interact with and phosphorylate RLA1/SMOS1 to reduce its stability. These results demonstrate that RLA1/SMOS1 acts as an integrator of the transcriptional complex directly downstream of GSK2 and plays an essential role in BR signaling and plant development in rice.

Treatment of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutation with EGFR-TKIs has achieved great success, yet faces the development of acquired resistance as the major obstacle to long-term disease remission in the clinic. MET (or c-MET) gene amplification has long been known as an important resistance mechanism to first-or second-generation EGFR-TKIs in addition to the appearance of T790 M mutation. Recent preclinical and clinical studies have suggested that MET amplification and/or protein hyperactivation is likely to be a key mechanism underlying acquired resistance to third-generation EGFR-TKIs such as osimertinib as well, particularly when used as a first-line therapy. EGFR-mutant NSCLCs that have relapsed from first-generation EGFR-TKI treatment and have MET amplification and/or protein hyperactivation should be insensitive to osimertinib monotherapy. Therefore, combinatorial therapy with osimertinib and a MET or even a MEK inhibitor should be considered for these patients with resistant NSCLC carrying MET amplification and/or protein hyperactivation.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer and frequently metastasizes to LNs. Identifying metastasis-promoting factors is of immense clinical interest, as the prognosis for patients with even a single unilateral LN metastasis is extremely poor. Here, we report that p90 ribosomal S6 kinase 2 (RSK2) promotes human HNSCC cell invasion and metastasis. We determined that RSK2 was overexpressed and activated in highly

Leaf erectness is key in determining plant architecture and yield, particularly in cereal crops. Brassinosteroids (BRs) play a unique role in controlling this trait in monocots, but the underlying cellular and molecular mechanisms remain big mysteries. Here we report that the abaxial sclerenchyma cell number of rice lamina joints (LJs) is closely related to leaf erectness, and BR signaling tightly regulates their proliferation. We identified a rice U-type cyclin CYC U4;1 enriched in rice LJs, with its expression accompanying LJ development. Genetic and biochemical studies demonstrated that CYC U4;1 plays a positive role in promoting leaf erectness by controlling the abaxial sclerenchyma cell proliferation. Furthermore, BR signaling inhibits the abaxial sclerenchyma cell division by coordinately regulating CYC U4;1 expression through BES1 and CYC U4;1 protein activity through GSK3 kinases. These results support a key role of the cyclin CYC U4;1 in mediating BR-regulated cell division to control leaf erectness.