Our results indicated that ERalpha and ERbeta were expressed in both gastric cancer and corresponding normal tissues. ERalpha expression and the absence of ERbeta expression are associated with poor survival.

Obesity is involved in tumor progression. However, the corresponding mechanisms remain largely unknown. Here, we report that adipocytes increase the invasive ability of tumor cells by producing exosomes with a high level of MMP3. Compared with 3T3-L1 cells, 3T3-L1 adipocytes are enriched in MMP3 protein and can transfer MMP3 to 3LL lung cancer cells. Then, MMP3 activates MMP9 activity in 3LL cells and promotes invasion in vitro and in vivo via MMP9. Furthermore, MMP3 protein levels in lung tumor tissues from obese patients are increased compared with those of non-obese patients. In addition, MMP3 protein levels are positively correlated with MMP9 activity in tumor tissues. Therefore, our results reveal a novel mechanism in the adipocyte-derived exosome-mediated promotion of lung tumor metastasis, which extends our knowledge regarding obesity and tumor progression.

LZTFL1 suppresses GC cell EMT by inhibiting β-catenin nuclear translocation. Re-expression of LZTFL1 in GC cells may be a potential therapeutic means to prevent GC metastasis.

With the improved understanding of the molecular pathogenesis and characteristics of cancers, the critical role of the immune system in preventing tumor development has been widely accepted. The understanding of the relationship between the immune system and cancer progression is constantly evolving, from the cancer immunosurveillance hypothesis to immunoediting theory and the delicate balance in the tumor microenvironment. Currently, immunotherapy is regarded as a promising strategy against cancers. Although adoptive cell therapy (ACT) has shown some exciting results regarding the rejection of tumors, the effect is not always satisfactory. Cellular therapy with CD4 + T cells remains to be further explored since the current ACT is mainly focused on CD8 + cytotoxic T lymphocytes (CTLs). Recently, Th9 cells, a subgroup of CD4 + T helper cells characterized by the secretion of IL-9 and IL-10, have been reported to be effective in the elimination of solid tumors and to exhibit superior antitumor properties to Th1 and Th17 cells. In this review, we summarize the most recent advances in the understanding of Th9 cell differentiation and the dual role, both anti-tumor and pro-tumor effects, of Th9 cells in tumor progression.

Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes T H 9 cell differentiation by activating NF-κB via Ca 2+ -dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas - induced T H 9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing T H 9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated T H 9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high T H 9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4 + T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for T H 9 cell induction and cancer therapy.

Abstract.The relationship between estrogen receptor (ER)α and patient prognosis has been identified in gastric cancer; however, the definite role of ERα in gastric cancer remains to be fully elucidated. The aim of the present in vitro study was to investigate the impact of ERα on cell proliferation, migration and invasion in gastric cancer cell lines. We investigated the biological effect of ERα overexpression on gastric carcinoma cells. An MKN28 gastric cancer cell line stably overexpressing ERα was established. The effect of ERα overexpression on cell growth was assessed by evaluating cell survival, colony formation, cell cycle progression and apoptosis. Cell migration and invasion were detected by Transwell migration/invasion assays. The protein levels of several potentially involved genes were determined by western blotting to elucidate the underlying molecular mechanisms. The Student's t-test was used to determine the statistical differences between various experimental and control groups, and one-way ANOVA test was used to determine the difference between three or more groups. The results showed that ERα overexpression significantly inhibited cell growth and proliferation, blocked cell entry into the G1/G0 phase and promoted cell apoptosis. In addition, ERα reduced the motility and invasion of gastric cancer cells. These phenotypes may partly be explained by a decrease in β-catenin expression caused by ERα overexpression. ERα overexpression effectively inhibited cell growth and cancer progression by suppressing β-catenin in gastric cancer, identifying ERα as a promising target with therapeutic potential for development of new approaches to treat gastric cancer.

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Current endocrine therapies for females with estrogen receptor-positive breast cancer have facilitated substantial improvements in outcomes. The effectiveness of endocrine therapy is limited by either initial de novo resistance or acquired endocrine resistance. Multiple mechanisms responsible for endocrine resistance have been proposed, including deregulation of various components of the estrogen receptor (ER) pathway, alterations in cell cycle and cell survival signaling molecules, and the activation of escape pathways. Dysregulation of miRNA expression has been associated with experimental and clinical endocrine therapy resistance. miRNAs are pivotal to understanding the complex biological mechanism of endocrine resistance, and may serve as novel candidate predictive and prognostic surrogates and therapeutic targets. This review focuses on current progress concerning the roles of miRNAs in endocrine resistance, and discusses the challenges and opportunities for implementing miRNA-based assays and treatment for patients with endocrine-resistant breast cancer.