CD19 chimeric antigen receptor T (CD19CAR-T) cells have achieved promising outcomes in relapsed/refractory B cell malignancies. However, recurrences occur due to the loss of CAR-T persistence. We developed dual T/B co-stimulatory molecules (CD28 and CD40) enhance intense tumoricidal activity CD19.28.40z promoted pNF-κB pRelB downstream signaling while diminishing NFAT upon exposure. demonstrated greater proliferation, which translated into effective anti-tumor cytotoxicity long-term...

Abstract Genetic alterations in the RUNX family genes and their co-factor CBFB are frequently observed cancer. In breast cancer, RUNX1 identified as significantly mutated genes, while RUNX3 expression is often silenced through hypermethylation. These observations highlight importance of mammary homeostasis. Previous studies on luminal-type cancer demonstrated that restoration inhibits tumor progression by destabilizing estrogen receptor α (ERα) protein. However, despite therapeutic promise...

Abstract Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition RUNX3 in gastric cell lines reduced migration, invasion, and anchorage-independent growth vitro. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression xenograft liver metastasis. We interrogated the potential as driver by profiling its target genes. Transcriptomic analysis revealed strong involvement regulation multiple developmental pathways, consistent with notion...

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain HGF (scHGF); however, only proteolytically processed two-chain (tcHGF) can activate the MET receptor. We investigated localization of tcHGF and activated/phosphorylated (pMET) using a tcHGF-specific antibody. In day 16.5 mouse embryos, total (scHGF + tcHGF) was mainly localized in smooth muscle cells close to, but separate from, MET-positive epithelial endodermal organs, including stomach. adult stomach, cells, glandular...

Abstract Aberrant activation of the MET /hepatocyte growth factor ( HGF ) receptor participates in malignant behavior cancer cells, such as invasion‐metastasis and resistance to molecular targeted drugs. Many mutations extracellular region have been reported, but their significance is largely unknown. Here, we report dysregulation mutant originally found a lung patient with Val370 Asp370 (V370D) replacement located SEMA domain. ‐knockout cells were prepared reconstituted WT ‐ or V370D‐ ....

Peripheral T-cell lymphoma (PTCL) is a type of non-Hodgkin that progresses aggressively with poor survival rate. CAR T cell targeting receptor β-chain constant domains 1 (TRBC1) malignant cells has been developed recently by using JOVI.1 monoclonal antibody as template. However, the mode binding still unknown. This study aimed to investigate molecular interaction between and TRBC1 computational methods docking. Therefore, TRBC protein crystal structures (TRBC1 TRBC2) well sequences CDR were...

<p>The excel file shows active RUNX3 binding sites enriched with CDX2, LHX2 and TCF3 motifs their corresponding GO biological processes at the Pages 1, 2 3, respectively.</p>

<p>The excel file shows active RUNX3 binding sites enriched with CDX2, LHX2 and TCF3 motifs their corresponding GO biological processes at the Pages 1, 2 3, respectively.</p>

<p>Higher RUNX3 expression in gastric cancer patients is associated with advanced stage and disease progression A, B, TCGA patient dataset visualized by XENA software (UCSC, n=591). Comparison of the mRNA between normal tissues (n=38) primary tumors (n=411) (A) as well Ia (n=17) IV (n=49) (B) are shown; **, P < 0.01 *, 0.05 a two-tailed Student t test. C, from microarray (cBioPortal) was obtained to determine disease-free (n=22) or recurrence (n=5); D, comparison survival data high...

<p>RUNX3 drives a metastatic transcriptional program. <b>A,</b> A volcano plot obtained from RNA-seq. total of 1,005 genes significantly downregulated (<i>P</i> < 0.05) in RUNX3 KO cells were identified, including CD44, Vimentin, IGFBP3, and WNT5A (marked red). 554 upregulated GPNMB blue). All dots are visualized on the basis expression alteration by ≥2-fold change KO. <b>B,</b> Analysis enriched pathway MSIgDB Hallmark 2020 Gene Ontology...

<p>RUNX3 drives metastasis in gastric cancer cells. <b>A,</b> Subcutaneous xenograft tumors were obtained by inoculation of 1 × 10<sup>6</sup> HGC-27 control and RUNX3 KO cells, respectively. Typical images are shown (<i>n</i> = 5). <b>B,</b> The weight was quantified; ****, <i>P</i> < 0.0001 a two-tailed Student <i>t</i> test. <b>C,</b> Liver model splenic Representative liver control, KO, rescued...

<div>Abstract<p>Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition RUNX3 in gastric cell lines reduced migration, invasion, and anchorage-independent growth <i>in vitro</i>. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression xenograft liver metastasis. We interrogated the potential as driver by profiling its target genes. Transcriptomic analysis revealed strong involvement regulation multiple...

<div>Abstract<p>Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition RUNX3 in gastric cell lines reduced migration, invasion, and anchorage-independent growth <i>in vitro</i>. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression xenograft liver metastasis. We interrogated the potential as driver by profiling its target genes. Transcriptomic analysis revealed strong involvement regulation multiple...

<p>RUNX3 drives metastasis in gastric cancer cells. <b>A,</b> Subcutaneous xenograft tumors were obtained by inoculation of 1 × 10<sup>6</sup> HGC-27 control and RUNX3 KO cells, respectively. Typical images are shown (<i>n</i> = 5). <b>B,</b> The weight was quantified; ****, <i>P</i> < 0.0001 a two-tailed Student <i>t</i> test. <b>C,</b> Liver model splenic Representative liver control, KO, rescued...

<p>RUNX3 expression is higher in liver metastasis than the primary tumor splenic inoculation model A, RT-qPCR indicates relative RUNX3 obtained from tumors spleen and after of HGC-27 control cells; **, P < 0.01 by a two-tailed Student t test. B, representative images immunofluorescence study to compare cells. Imaging for KO cells also shown as negative control. Scale bar: 20 μm. C, quantitative analysis image-J fluorescence level test.</p>

<p>Histone modification and interactions proximal to genes transcriptionally activated by RUNX3. ChIP-seq analyses of histone RUNX3 binding sites in HGC-27 control (cont) KO cells are juxtaposed H3K27ac HiChIP analyses. The representative include <i>CD44, IGFBP3, VIM, WNT5A, DPYSL3</i>, <i>RUNX2</i>, based on the list that showed high scores <i>P</i> values profiles. Enhancer–promoter indicated loops. Arrowhead indicates change peak after KO.</p>

<p>RUNX3 promotes cancer cell migration and invasion. <b>A,</b> The efficiency of siRUNX3 KD in HGC-27 LMSU RUNX3 OE GAS24 were validated by immunoblot. <b>B,</b> Invasion analysis for also GAS24. Experiments repeated three times. Typical images from one experiment are shown. <b>C,</b> Cell invasion counted quantified 5 different high-power fields each experiment; ***, <i>P</i> < 0.001; **, 0.01; *, 0.05 a two-tailed Student...

<p>Addition of exogenous recombinant WNT5A restores migration and invasion abilities to RUNX3 KO cells A, WST-1 cell proliferation assay in HGC-27 after siRNA mediated KD; *, P < 0.05 by a two-tailed Student t test. B, immunoblot for treatment (0.1mg/mL) is shown. C, representative images LMSU siWNT5A, GAS24 Matrigel colony formation (top). The number was counted shown as fold change control (mean + SD); **, 0.01 test.</p>

<p>Histone modification and interactions proximal to genes transcriptionally activated by RUNX3. ChIP-seq analyses of histone RUNX3 binding sites in HGC-27 control (cont) KO cells are juxtaposed H3K27ac HiChIP analyses. The representative include <i>CD44, IGFBP3, VIM, WNT5A, DPYSL3</i>, <i>RUNX2</i>, based on the list that showed high scores <i>P</i> values profiles. Enhancer–promoter indicated loops. Arrowhead indicates change peak after KO.</p>

<p>Chromatin status relative to RUNX3 peaks at the WNT5A promoter Enlarged image of ChIPseq analysis locus in Fig. 4.</p>

<p>RUNX3 promotes cancer cell migration, invasion and anchorage independent growth in gastric cells A, RT-qPCR analysis for RUNX3 mRNA HGC-27 after KO; ****, P < 0.0001 by a twotailed Student t test. B, immunoblot shows absence of protein CRISPR/Cas9 mediated KO. C, WST-1 proliferation assay **, 0.01 two-tailed D, migration Experiments were repeated three times. Typical images from one experiment are shown. E, counted quantified 5 different high-power fields each experiment; ***,...

<p>RUNX3 drives a metastatic transcriptional program. <b>A,</b> A volcano plot obtained from RNA-seq. total of 1,005 genes significantly downregulated (<i>P</i> < 0.05) in RUNX3 KO cells were identified, including CD44, Vimentin, IGFBP3, and WNT5A (marked red). 554 upregulated GPNMB blue). All dots are visualized on the basis expression alteration by ≥2-fold change KO. <b>B,</b> Analysis enriched pathway MSIgDB Hallmark 2020 Gene Ontology...

<p>RUNX3 promotes cancer cell migration and invasion. <b>A,</b> The efficiency of siRUNX3 KD in HGC-27 LMSU RUNX3 OE GAS24 were validated by immunoblot. <b>B,</b> Invasion analysis for also GAS24. Experiments repeated three times. Typical images from one experiment are shown. <b>C,</b> Cell invasion counted quantified 5 different high-power fields each experiment; ***, <i>P</i> < 0.001; **, 0.01; *, 0.05 a two-tailed Student...

<p>WNT5A plays a pivotal role in RUNX3-mediated metastasis gastric cancer cells. <b>A,</b> immunoblot for WNT5A HGC-27 after RUNX3 KO, LMSU KD, and GAS24 OE is shown. <b>B,</b> Immunoblot siWNT5A, recombinant treatment (0.1 mg/mL). <b>C,</b> Invasion migration analysis siRNA mediated Experiments were repeated three times. Typical images from one experiment are shown (top). Cell invasion counted quantified 5 different high-power fields each (bottom);...

<p>RUNX3 expression is higher in liver metastasis than the primary tumor splenic inoculation model A, RT-qPCR indicates relative RUNX3 obtained from tumors spleen and after of HGC-27 control cells; **, P < 0.01 by a two-tailed Student t test. B, representative images immunofluorescence study to compare cells. Imaging for KO cells also shown as negative control. Scale bar: 20 μm. C, quantitative analysis image-J fluorescence level test.</p>