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The Marchenko method is a data-driven way that makes it possible to calculate Green’s functions from virtual points in the subsurface using the reflection data at the surface and requiring only a macro velocity model. This method requires collocated sources and receivers. However, in practice, irregular sampling of sources or receivers will cause gaps and distortions in the obtained focusing functions and Green’s functions. To solve this problem, this paper proposes to integrate a sparse inversion into the iterative Marchenko scheme. Specifically, we add sparsity constraints to the Marchenko equations and apply the sparse inversion during the iterative process. To reduce the strict requirements on acquisition geometries, our work deals with the situation in which the sources are subsampled where the integrations are carried out over the receivers, while the existing point spread function method solves the situation where the receivers are subsampled. We make a step to handle both situations at the same time by integrating this method with our work because of the same iterative framework. Our new method is applied to a two-dimensional numerical example with irregularly sampled data. The result shows that it can effectively fill gaps in the obtained focusing functions and Green’s functions in the Marchenko method.

Prostaglandins are among the most important natural isolates owing to their broad range of bioactivities and unique structures. However, current methods for the synthesis of prostaglandins suffer from low yields and lengthy steps. Here, we report a practicability-oriented synthetic strategy for the enantioselective and divergent synthesis of prostaglandins. In this approach, the multiply substituted five-membered rings in prostaglandins were constructed via the key enyne cycloisomerization with excellent selectivity (>20:1 d.r., 98% e.e.). The crucial chiral centre on the scaffold of the prostaglandins was installed using the asymmetric hydrogenation method (up to 98% yield and 98% e.e.). From our versatile common intermediates, a series of prostaglandins and related drugs could be produced in two steps, and fluprostenol could be prepared on a 20-gram scale.

The transition-metal-catalyzed asymmetric cycloisomerization of 1,7-enynes is regarded as a formidable challenge due to the poor ability of 1,7-enynes to serve as bidentate ligands to metal. In this Letter, a highly enantioselective rhodium(I)-catalyzed Alder-ene-type cycloisomerization of 1,7-enynes is disclosed, offering an efficient method for the synthesis of a wide range of fused six-membered cyclic compounds. Furthermore, a high turnover frequency experiment and deuterium-labeling experiment were performed to give insight into this transformation.

Heavy metals in groundwater and soil are toxic to humans. An accurate risk assessment of heavy metal contamination can aid in environmental security decision making. In this study, the improved ecological risk index (RI) is used to comprehensively investigate the influence of heavy metals in soil and groundwater within electroplating factories and their surrounding regions. In the non-overlapping area, the RI of soil and groundwater is computed individually, and in the overlapping area, the greater RI of soil and groundwater is employed. Two typical electroplating factories are used to examine the heavy metal distribution pattern. The heavy metal concentrations are compared between Factory A, which is in operation, and Factory B, which is no longer in operation, in order to analyze the heavy metal concentrations and associated ecological risks. Heavy metals continue to spread horizontally and vertically after Factory B was closed. Heavy metal concentrations in groundwater surrounding Factory B are substantially greater, and the maximum concentration exists deeper than in Factory A. Because Cr, Cu, and Hg in soil contribute significantly to the RI, the primary high RI region is observed at Factory A and the region to the southwest. The RI of Factory B demonstrates a broad, moderate risk zone in the west and southwest.

Prostaglandins are among the most significant natural isolates owing to their broad range of bioactivities and unique structures. However, the current synthesis of prostaglandins still suffers from low yields and lengthy steps. Here, We reported a practicability-oriented synthetic strategy for the enantioselective and divergent synthesis of PGs. In this approach, the multiply substituted five-membered rings in prostaglandins were constructed via the key Zhang enyne cycloisomerization with excellent selectivity (> 20:1 dr, 98% ee). The crucial chiral center on the scaffold of prostaglandins was installed using the asymmetric hydrogenation method (up to 98% yield and 98% ee). From our versatile common intermediates, a series of PGs and related drugs could be produced in two steps, and fluprostenol could be prepared on a 20-gram scale.

The mechanisms by which 2,5-hexanedione (2,5-HD) exposure adversely affects reproduction are unclear. In the present study, whole neonatal mouse ovaries were exposed to 2,5-HD in vitro and then assessed for progesterone levels to determine the effects of this compound on ovary function. Ovarian histomorphological analyses were performed to assess the effects of 2,5-HD on follicular development, and PI3K signaling pathway was evaluated to elucidate the molecular mechanisms of 2,5-HD-mediated toxicity on follicular development. The results showed that after ovarian exposure to 2,5-HD in vitro, the percentage of secondary follicles decreased, while the progesterone levels and the percentage of unhealthy follicles increased, with oocytes identified as the target of damage. The 2,5-HD treatment significantly decreased the of the gene encoding the apoptosis-related protein caspase-8, and PI3K/AKT/FOXO3 pathway signaling was also altered. Furthermore, the effects of 2,5-HD on the gene expression of the PI3K/AKT/FOXO3 and follicular development were blocked by 740Y-P (a PI3K activator), miR-214-3p was abnormally expressed, and luciferase reporter assay results demonstrated that the 3' untranslated region of PI3K was a direct target of miR-214-3p. Overall, the results of the present study indicate that 2,5-HD exposure inhibits follicular development, and the underlying mechanism may involve interference with miR-214-3p-mediated regulation of the PI3K signaling pathway.

Breast cancer is a highly heterogeneous disease that consists of subtypes with distinct genetic features and clinical symptoms. The patients with different subtypes react to different therapies, thus identifying molecular subtypes greatly contributes to precision diagnosis and personalized cancer treatment. PAM50 subtype is a widely accepted standard in breast cancer classification. The large amount of multi-omics data in public database like TCGA greatly contribute to the study of breast cancer subtype identification. However, the imbalance of sample subtypes in the existing database results in a large difficulty in correctly identifying subtypes with small sample size. In this paper, we proposed a novel method to accurately identify the PAM50 subtypes by utilizing the patients' omics profiles in TCGA database. Based on the integrated expression profiles of RNA-seq and Copy Number Alteration (CNA), the proposed method identifies subtype-related patterns by a multi-layer Convolutional Neural Network (CNN). A weighted loss function was applied to alleviate the effects of imbalanced samples, thus contributing to the accurate identification. We demonstrated that our method could identify PAM50 subtypes of patients with high precision (90.02%) and outperformed two benchmark methods.

Nanopore sequencing is promising because of its long read length and high speed. During sequencing, a strand of DNA/RNA passes through a biological nanopore, which causes the current in the pore to fluctuate. During basecalling, context-dependent current measurements are translated into the base sequence of the DNA/RNA strand. Accurate and fast basecalling is vital for downstream analyses such as genome assembly and detecting single-nucleotide polymorphisms and genomic structural variants. However, owing to the various changes in DNA/RNA molecules, noise during sequencing, and limitations of basecalling methods, accurate basecalling remains a challenge. In this paper, we propose Causalcall, which uses an end-to-end temporal convolution-based deep learning model for accurate and fast nanopore basecalling. Developed on a temporal convolutional network (TCN) and a connectionist temporal classification decoder, Causalcall directly identifies base sequences of varying lengths from current measurements in long time series. In contrast to the basecalling models using recurrent neural networks (RNNs), the convolution-based model of Causalcall can speed up basecalling by matrix computation. Experiments on multiple species have demonstrated the great potential of the TCN-based model to improve basecalling accuracy and speed when compared to an RNN-based model. Besides, experiments on genome assembly indicate the utility of Causalcall in reference-based genome assembly.

In this study, graphene wrapped Fe-doped TiO2 (G-TiO2-Fe) spheres were prepared through a simple hydrothermal process. The structural, optical and photocatalytic properties of synthesized composite were characterized by field emission scanning electron microscope (FE-SEM), X-ray diffraction (XRD), Raman Microprobe (Raman), X-ray photoelectron spectroscopy (XPS) and UV–Vis diffuse reflectance spectrophotometer (DRS). The G-TiO2-Fe composite showed a significant red-shift in light response edge as compared with TiO2. Meanwhile, the band gap exhibited an obvious decline from 3.24 to 2.99 eV. The photocatalytic capacity of G-TiO2-Fe was further evaluated by methylene blue (MB) degradation experiments, and the results indicated that the optimized G-TiO2-Fe exhibited a remarkable increase in photocatalytic activity. The superior photocatalytic performance of the novel material could be ascribed to the synthetic effects of doped Fe and wrapped graphene shells. The unique geometrical configuration and constructive component which modified the TiO2 electronic structure will largely improve the electron transporting efficiency and restrain the electron-hole recombination.

Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi and MEKi) therapies have markedly improved the clinical outcomes of patients with metastatic melanoma. Unfortunately, the efficacy of these treatments is often countered by the acquisition of drug resistance. Here we investigated the molecular mechanisms that underlie acquired resistance to BRAFi and to the combined therapy. Consistent with previous studies, we show that resistance to BRAFi is mediated by ERK pathway reactivation. Resistance to the combined therapy, however, is mediated by mechanisms independent of reactivation of ERK in many resistant cell lines and clinical samples. p21-activated kinases (PAKs) become activated in cells with acquired drug resistance and have a pivotal role in mediating resistance. Our screening, using a reverse-phase protein array, revealed distinct mechanisms by which PAKs mediate resistance to BRAFi and the combined therapy. In BRAFi-resistant cells, PAKs phosphorylate CRAF and MEK to reactivate ERK. In cells that are resistant to the combined therapy, PAKs regulate JNK and β-catenin phosphorylation and mTOR pathway activation, and inhibit apoptosis, thereby bypassing ERK. Together, our results provide insights into the molecular mechanisms underlying acquired drug resistance to current targeted therapies, and may help to direct novel drug development efforts to overcome acquired drug resistance.

Full Waveform Inversion (FWI) can be used to build high resolution velocity models, but there are still many challenges in seismic field data processing. The most difficult problem is about how to recover long-wavelength components of subsurface velocity models when seismic data is lacking of low frequency information and without long-offsets. To solve this problem, we propose to use Waveform Mode Decomposition (WMD) method to reconstruct low frequency information for FWI to obtain a smooth model, so that the initial model dependence of FWI can be reduced. In this paper, we use adjoint-state method to calculate the gradient for Waveform Mode Decomposition Full Waveform Inversion (WMDFWI). Through the illustrative numerical examples, we proved that the low frequency which is reconstructed by WMD method is very reliable. WMDFWI in combination with the adaptive multi-step inversion strategy can obtain more faithful and accurate final inversion results. Numerical examples show that even if the initial velocity model is far from the true model and lacking of low frequency information, we still can obtain good inversion results with WMD method. From numerical examples of anti-noise test, we see that the adaptive multi-step inversion strategy for WMDFWI has strong ability to resist Gaussian noise. WMD method is promising to be able to implement for the land seismic FWI, because it can reconstruct the low frequency information, lower the dominant frequency in the adjoint source, and has a strong ability to resist noise.

Cobalt nanoparticles (CoNPs) have been widely used in industry given their physical, chemical and magnetic properties; however, CoNPs may cause neurological symptoms and diseases in human, yet their mechanisms of toxicity remain unknown. Here, we used male Wistar rats to investigate differences in the toxic effects associated with CoNPs and CoCl2. Upon exposure to CoCl2, and 96 nm or 123 nm CoNPs at the same concentration, the Co2+ content in CoCl2 group was significantly higher than that in either the CoNPs groups in brain tissues and blood, but lower in liver. Significant neural damage was observed in both hippocampus and cortex of the temporal lobe. Increase malondialdehyde (MDA) content and CASPASE 9 protein level were associated both with CoCl2 and CoNPs treatments, consistent with lipid perioxidation and apoptosis. Heme oxygenase-1 and (NF-E2) p45-related factor-2 protein levels were elevated in response to 96 nm CoNPs exposure. In PC12 cells, NRF2 downregulation led to reduced cell viability and increased apoptotic rate. In conclusion, both CoNPs and CoCl2 cause adverse neural effects, with nanoparticles showing greater neurotoxic potency. In addition, NRF2 protects neural cells from damage induced by CoCl2 and CoNPs by activating downstream antioxidant responses.

As the most commonly used plasticizer, Di-(2-ethylhexyl)-phthalate (DEHP) exists everywhere in the environment due to the widespread use of polyvinyl chloride (PVC) in human life, and it is also a recognized environmental pollutant. Studies have proved the hepatotoxicity of DEHP, however the mechanism has not been adequately explored, especially the role of the reactive oxygen species (ROS) in it. In the present study, 21 day-old ICR mice were administered DEHP with dose of 0, 125, 250, and 375 mg/kg/day for 28 days by intragastrical gavage. After contamination, histopathology displayed that liver tissue were damaged mildly with the effect of DEHP, a significant increase of the serum liver function index (including aspartate transaminase (AST) and alanine transaminase (ALT)) were observed. Additionally, the level of lipid peroxidation markedly rise, especially ROS and malondialdehyde (MDA), but the activation of superoxide dismutase (SOD) was obviously decreased in mice liver. In addition, DEHP promoted the phosphorylation of JNK and p38MAPK proteins in mice liver, as well as increased the expression of p53 protein and decreased the level of DNA methylation in the p53 gene promoter region. These results indicated that the hepatotoxicity of mice caused by DEHP may be through activating the JNK/p38MAPK/p53 signaling pathway and further promoting the generation of ROS to induce lipid peroxidation in liver, and the role of DNA methylation may be inevitable.

Surface integrity determines the performance and quality of the end product. It often needs to change the input parameters, such as cutting parameter, cutting tool geometry and material, and tool coating, to obtain the best machining surface integrity. This article presents and demonstrates the effectiveness for the multi-objective optimization of cutter geometric parameters for surface integrity of milling Ti-5Al-5Mo-5V-1Cr-1Fe titanium alloy via grey relational analysis coupled with the Taguchi method, entropy weight method, and analytic hierarchy process. The main influence factors are chosen as radial rake angle, primary radial relief angle, and helix angle, while surface roughness and residual stress are taken as performance characteristics. Based on the Taguchi method, an L16 (43) orthogonal array is chosen for the experiments. The effect of cutter geometric parameters on surface roughness and residual stress is analysed by signal-to-noise ratio. Then, the multiple objectives optimization problem is successfully converted to a single-objective optimization of grey relational grade with the grey relational analysis. The weight coefficient for grey relational grade is determined by entropy weight method integrated with analytic hierarchy process. The results show that the order of importance for controllable factor to the milling surface integrity, in sequence, is radial rake angle, primary radial relief angle, and helix angle. The validation experiment verifies that the proposed optimization method has the ability to find out the optimal geometric parameters in terms of milling surface integrity.

Melanoma patients with oncogenic BRAF(V600E) mutation have poor prognoses. While the role of BRAF(V600E) in tumorigenesis is well established, its involvement in metastasis that is clinically observed in melanoma patients remains a topic of debate. Here, we show that BRAF(V600E) melanoma cells have extensive invasion activity as assayed by the generation of F-actin and cortactin foci that mediate membrane protrusion, and degradation of the extracellular matrix (ECM). Inhibition of BRAF(V600E) blocks melanoma cell invasion. In a BRAF(V600E)-driven murine melanoma model or in patients' tumor biopsies, cortactin foci decrease upon inhibitor treatment. In addition, genome-wide expression analysis shows that a number of invadopodia-related genes are downregulated after BRAF(V600E) inhibition. Mechanistically, BRAF(V600E) induces phosphorylation of cortactin and the exocyst subunit Exo70 through ERK, which regulates actin dynamics and matrix metalloprotease secretion, respectively. Our results provide support for the role of BRAF(V600E) in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma.

Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi+MEKi) therapies have significantly improved clinical outcomes in patients with metastatic melanoma. Unfortunately, the efficacy is beset by the acquisition of drug resistance1–6. Here we investigated molecular mechanisms underlying acquired resistance to BRAFi (BRAFi resistance, “BR”) and BRAFi+MEKi (combination therapy resistance, “CR”). Consistent with previous studies, BR is mediated by ERK pathway re-activation. CR is, however, mediated by mechanisms independent of re-activation of ERK in many therapy-resistant cell lines and clinical samples. p21-activated kinases (PAKs) become activated in acquired drug resistant cells and play a pivotal role in mediating both BR and CR. Our screening using reverse phase protein array (RPPA) revealed distinct mechanisms by which PAKs mediate BR and CR. In BR, PAKs phosphorylate CRAF and MEK to reactivate ERK. In CR, PAKs regulate JNK and β-catenin phosphorylation, mTOR pathway activation, and inhibit apoptosis, thereby bypassing ERK. Together, our results provide new insights into molecular mechanisms underlying acquired drug resistance to current targeted therapies, and may help to direct novel drug development efforts to overcome acquired drug resistance.

Due to the wide use of silver nanoparticles (AgNPs) in various fields, it is crucial to explore the potential negative impacts on the aquatic environment of AgNPs entering into the environment in different ways. In this study, comparative experiments were conducted to investigate the toxicological impacts of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) with two kinds of dosing regimens, continuous and one-time pulsed dosing, in different exposure media (deionized water and XiangJiang River water). There were a number of quite different experimental results (including 100% mortality of zebrafish, decline in the activity of enzymes, and lowest number and length of adventitious roots) in the one-time pulsed dosing regimen at high PVP-AgNP concentration exposure (HOE) compared to the three other treatments. Meanwhile, we determined that the concentration of leached silver ions from PVP-AgNPs was too low to play a role in zebrafish death. Those results showed that HOE led to a range of dramatic ecosystem impacts which were more destructive than those of other treatments. Moreover, compared with the continuous dosing regimen, despite the fact that higher toxicity was observed for HOE, there was little difference in the removal of total silver from the aquatic environment for the different dosing regimens. No obvious differences in ecological impacts were observed between different water columns under low concentration exposure. Overall, this work highlighted the fact that the toxicity of AgNPs was impacted by different dosing regimens in different exposure media, which may be helpful for assessments of ecological impacts on aquatic environments.

Polarized exocytosis is generally considered as the multistep vesicular trafficking process in which membrane-bounded carriers are transported from the Golgi or endosomal compartments to specific sites of the plasma membrane. Polarized exocytosis in cells is achieved through the coordinated actions of membrane trafficking machinery and cytoskeleton orchestrated by signaling molecules such as the Rho family of small GTPases. Elucidating the molecular mechanisms of polarized exocytosis is essential to our understanding of a wide range of pathophysiological processes from neuronal development to tumor invasion.

In order to fabricate a tissue scaffold with the neurotrophic and electrical activities, conductive nerve growth factor (NGF)-conjugated polypyrrole-poly(l-lactic acid) (PPy-PLLA) composite fibers were prepared by oxidation polymerization and EDC chemistry with poly-l-lysine. PPy nanoparticles (∼70nm diameter) accumulated on PLLA fiber surface to form a rough thick shell (∼200nm thickness). These NGF-conjugated PPy-PLLA fibers could support PC12 neurite outgrowth and extension. Especially, 40% and 74% increase in PC12 neurite outgrowth and extension, respectively, could be obtained under electrical stimulation of 100mV/cm voltages through the composite fibers. A mechanism for the interaction between neurite extension and the NGF-conjugated PPy-PLLA fibers under electro-stimulation was proposed, to explain the synergistic effect of the rough PPy shell, conjugated NGF and electricity on neurite outgrowth and elongation.

In order to obtain magnetic nanoparticles (NPs) coated with small biomolecules, histidine (His)-coated iron oxide (His-Fe 3 O 4 ) and cobalt ferrite (His-CoFe 2 O 4 ) with a polycrystalline structure were prepared by a simple liquid deposition method at room temperature. The growth mechanism for His-Fe 3 O 4 and His-CoFe 2 O 4 NPs was preliminarily explained, and their growth conditions, such as His concentrations, Co/Fe ratio, the synthesis time, were studied. The analysis of Fourier transform infrared spectra and X-ray photoelectron spectroscopy results indicated that the as-prepared particles were conjugated with the small histidine molecules. The hysteresis loops of NPs revealed their good magnetic property. L929 Cell tests indicate the good cytocompatibility of His-Fe 3 O 4 and His-CoFe 2 O 4 NPs, which is better than the previous prepared magnetic NPs with the polymer.

Silk fibroin (SF)-coated Fe(3)O(4) nanoparticles (NPs) with good superparamagnetism were successfully prepared via a bio-mineralization process at room temperature. Two cell tests revealed that mineralized SF-coated Fe(3)O(4) NPs presented good cytocompatibility for L929 and osteoblast cells and higher cell density after 5 d with high concentrations of SF-coated Fe(3)O(4) NPs (up to 0.5 mg/mL). These resulted from SF surface coating on NPs, nano-surface morphology and iron ion release of Fe(3)O(4) NPs. The mineralized SF-coated Fe(3)O(4) NPs could be envisioned for various bone orthopedic and therapeutic applications, in which SF-coated NPs location is controlled through an external magnetic field to promoted bone growth.

During the past 2 years, an atypical clinical outbreak, caused by a highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) with a unique 30-amino-acid deletion in its Nsp2-coding region, was pandemic in China. In this study, we generated four full-length infectious cDNA clones: a clone of the highly virulent PRRSV strain JXwn06 (pWSK-JXwn), a clone of the low-virulence PRRSV strain HB-1/3.9 (pWSK-HB-1/3.9), a chimeric clone in which the Nsp2 region containing the 30-amino-acid deletion was replaced by the corresponding region of the low-virulence PRRSV strain HB-1/3.9 (pWSK-JXwn-HB1nsp2), and a mutated HB-1/3.9 clone with the same deletion in Nsp2 as JXwn06 (pWSK-HB1-ND30). We also investigated the pathogenicities of the rescued viruses (designated RvJXwn, RvJXwn-HB1nsp2, RvHB-1/3.9, and RvHB1-ND30, respectively) in specific-pathogen-free piglets in order to determine the role of the 30-amino-acid deletion in the virulence of the highly pathogenic PRRSV. All the rescued viruses could replicate stably in MARC-145 cells. Our findings indicated that RvJXwn-HB1nsp2 retained high virulence for piglets, like RvJXwn and the parental virus JXwn06, although the survival time of piglets infected with RvJXwn-HB1nsp2 was obviously prolonged. RvHB1-ND30 exhibited low virulence for piglets, like RvHB-1/3.9 and the parental virus HB-1/3.9. Therefore, we conclude that the 30-amino-acid deletion is not related to the virulence of the highly pathogenic PRRSV emerging in China.

Regulatory T lymphocytes (T-regs) may be involved in suppressing the host's immunity, which is important for viral clearance, and may therefore contribute to persistent viral infection. However, nothing is known regarding the situation of porcine T-regs during persistent infection with porcine reproductive and respiratory syndrome virus (PRRSV). This study, which used flow cytometry and real-time PCR, determined that the frequencies of CD4+CD25+ T-cells and porcine Forkhead/winged helix transcription factor (FoxP3) mRNA levels in peripheral blood significantly increased during PRRSV persistence, indicating that CD4+CD25+ T-regs might play an important role in PRRSV persistent infection. This study contributes to a better understanding of the immunological basis of PRRSV persistence.

Porcine reproductive and respiratory syndrome virus (PRRSV) is characteristic of genetically extensive variation. The objective of the present study was to analyze the molecular variation and evolution of porcine reproductive and respiratory syndrome virus in China based on the complete genomic sequences of three highly pathogenic Chinese PRRSV strains isolated in 2006 and the sequences of the amplified Nsp2, ORF5 and ORF7 genes from clinical specimens during 2006-2008. Full-length genome sequencing and phylogenetic analysis showed that the three strains (JXwn06, BJsy06 and NX06) had a unique 30-amino-acid discontinuous deletion in Nsp2, and were classified into the same subgroup that consisted of the most Chinese strains isolated during 2006-2007, the pandemic period of atypical PRRS. The evolution analysis suggested that the emergence of the highly pathogenic PRRSV in China experienced a gradual variation and evolution accumulation progress from Chinese domestic virus. The variation analysis of the amplified 41 Nsp2, 59 ORF5 and 59 ORF7 genes indicated that the diversity of PRRSV strain existed in the field, and the highly pathogenic PRRSV strain with the 30-amino-acid deletion in Nsp2 was the dominating virus in China in recent years. Our data contribute to the understanding of molecular variation and epidemiology surveillance of PRRSV in China.

Summary Epithelial-mesenchymal transition (EMT) is an important developmental process hijacked by cancer cells for their dissemination. Here, we show that Exo70, a component of the exocyst complex, undergoes isoform switching mediated by ESRP1, a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial isoform of Exo70 affects the levels of key EMT transcriptional regulators such as Snail and ZEB2 and is sufficient to drive the transition to epithelial phenotypes. Differential Exo70 isoform expression in human tumors correlates with cancer progression, and increased expression of the epithelial isoform of Exo70 inhibits tumor metastasis in mice. At the molecular level, the mesenchymal—but not the epithelial—isoform of Exo70 interacts with the Arp2/3 complex and stimulates actin polymerization for tumor invasion. Our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for EMT and tumor invasion.