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The leaves of Emmenopterys henryi Oliv. cultured under 25°C/20°C (CK) and 42◦C/37◦C (heat stress, HS), respectively, were used for physiological and transcriptomic analysis based on RNA-seq technology. Results showed that net photosynthesis rate (PN), ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity, chlorophyll and brassinosteroid (BR) content, and leaf angle (LA) decreased significantly while the contents of H2O2, thiobarbituric acid reactive substance (TBARS), abscisic acid (ABA) and anthocyanin, and the activities of superoxide dismutase (SOD), catalase (CAT), guajacol-dependent peroxidase (POD), ascorbate peroxidase (APX) increased obviously under HS. RNA-seq analysis indicated that 9492 differentially expressed genes (DEGs) were found, of which 4368 were up-regulated and 5124 were down-regulated. The most enriched KEGG pathways of DEGs were photosynthesis, plant hormone signal transduction, secondary metabolites biosynthesis. HSPs, SOD, CAT, POD, APX were up-regulated whereas genes related to photosystem I (PSI) and photosystem II (PSII) light-harvesting complex and reaction center proteins, cytochrome b6-f complex, plastocyanin, ATP synthase, Rubisco, Rubiscoactivase (RCA), and chlorophyll biosynthesis were down-regulated under heat stress. HS resulted in downregulation of genes related to BR biosynthesis and positive regulation in BR signaling but upregulation of genes related to inactivation of BR. Anthocyanin accumulation in E. henryi under HS might resulted from upregulation of PAL, CHI, DFR whereas downregulation of ANR and LAR. HS led to increase of ABA level but downregulation of genes related to ABA signaling. Transcription factors HSFA, HSFB and HSFC were involved in E. henryi HS response. E. henryi might responds to HS via regulating photosynthesis, antioxidase activity, ABA and BR metabolism and signaling, anthocyanin metabolism and HSPs and HSFs expression. [ABSTRACT FROM AUTHOR]

Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca2+ sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors. [ABSTRACT FROM AUTHOR]

Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics. [ABSTRACT FROM AUTHOR]

The skeleton is the most common metastatic site for breast cancer, with bone metastasis causing pain as well as risk of pathological fractures. Interaction between tumors and the bone microenvironment creates a vicious cycle that accelerates both bone destruction and cancer progression. This study is the first to analyze the soluble factors secreted by breast tumor-associated osteoblasts (TAOBs), which are responsible for promoting cancer progression. The addition of CXCL5 (chemokine (C-X-C motif) ligand 5), present in large amounts in TAOB-condition medium (TAOB-CM), mimicked the inductive effect of TAOB-CM on breast cancer epithelial-mesenchymal transition, migration and invasion. In contrast, inhibition of CXCL5 in OBs decreased TAOB-mediated cancer progression. Inducement of MCF-7 and MDA-MB-231 cancer progression by TAOB-derived CXCL5 is associated with increased Raf/MEK/ERK activation, and mitogen- and stress-activated protein kinase 1 (MSK1) and Elk-1 phosphorylation, as well as Snail upregulation. Activation of Elk-1 facilitates recruitment of phosphorylated MSK1, which in turn enhances histone H3 acetylation and phosphorylation (serine 10) of Snail promoter, resulting in Snail enhancement and E-cadherin downregulation. Moreover, mice treated with anti-CXCL5 antibodies showed decreased metastasis of 4T1 breast cancer cells. Our study suggests that inhibition of CXCL5-mediated ERK/Snail signaling is an attractive therapeutic target for treating metastases in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to detect postoperative persistent circulating tumour cells (CTCs) in stages II and III colon cancer patients undergoing curative resection and so identify a subgroup of patients who are at high risk for early relapse.Methods: Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in 141 stages II and III colon cancer patients undergoing curative resection to determine the significance of CTCs in postoperative early relapse.Results: Out of 141 patients, postoperative early relapse and non-early relapse/no relapse was found in 48 (34.0%) patients and 93 (66.0%) patients, respectively. Univariately, postoperative early relapse was significantly correlated with lymph node metastasis (P=0.025), vascular invasion (P=0.002), perineural invasion (P=0.001), laparoscopic surgery (P=0.019), high postoperative serum CEA levels (P=0.001), and presence of persistent postoperative CTCs (P<0.001). Using a multivariate proportional hazards regression analysis, the presence of perineural invasion (P=0.034; HR, 1.974; 95% CI: 1.290-3.861), high postoperative serum CEA levels (P=0.020; HR, 2.377; 95% CI: 1.273-4.255), and the presence of persistent postoperative CTCs (P<0.001; HR, 11.035; 95% CI: 4.396-32.190), were demonstrated to be independent predictors for postoperative early relapse. Furthermore, the presence of persistent postoperative CTCs was strongly correlated with a poorer disease-free and overall survival (both P<0.001).Conclusions: This study suggests that molecular detection of persistent postoperative CTCs is a prognostic predictor of early relapse in UICC stage II/III colon cancer patients, and thus could help to define patients with this tumour entity for an enhanced follow-up and therapeutic program. [ABSTRACT FROM AUTHOR]

A case of lethal, subacute monocytic leukaemia is described in which the development of multiple sclerotic bone lesions, resembling metastases, was due to secondary myeloid metaplasia. The spectrum of leukaemic involvement of the skeleton is discussed with emphasis on sclerotic bone lesions. The differential diagnosis of other focal areas of bone sclerosis is considered. [ABSTRACT FROM AUTHOR]