Transforming growth factor beta (TGF-β) is a multi-functional polypeptide that plays a critical role in regulating a broad range of cellular functions and physiological processes. Signaling is initiated when TGF-β ligands bind to two types of cell membrane receptors with intrinsic Ser/Thr kinase activity and transmitted by the intracellular Smad proteins, which act as transcription factors to regulate gene expression in the nucleus. Although it is relatively simple and straight-forward, this TGF-β/Smad pathway is regulated by various feedback loops at different levels, including the ligand, the receptor, Smads and transcription, and is thus fine-tuned in terms of signaling robustness, duration, specificity, and plasticity. The precise control gives rise to versatile and context-dependent pathophysiological functions. In this review, we firstly give an overview of TGF-β signaling, and then discuss how each step of TGF-β signaling is finely controlled by distinct modes of feedback mechanisms, involving both protein regulators and miRNAs.

Chemokine (C-C motif) ligand 7 (CCL7), a CC chemokine, is a chemotactic factor and attractant for various kinds of leukocytes, including monocytes and neutrophils. CCL7 is widely expressed in multiple cell types and can participate in anti-inflammatory responses through binding to its receptors to mediate the recruitment of immune cells. Abnormal CCL7 expression is associated with certain immune diseases. Furthermore, CCL7 plays a pivotal role in tumorigenesis. CCL7 promotes tumor progression by supporting the formation of the tumor microenvironment and facilitating tumor invasion and metastasis, although some studies have suggested that CCL7 has tumor suppressor effects. In this review, we summarize the currently available information regarding the influence of CCL7 on tumors.

A lignan-rich diet is associated with a lower risk of human breast cancer. Enterolactone, an active polyphenol metabolites of lignan, was reported to have an antitumor effect. We investigated the mechanism for the effect of enterolactone against human breast cancer. Cellular changes, and associated genes induced by enterolactone, were investigated in MDA-MB-231 cells. Enterolactone showed an antiproliferative effect, and its IC50 was 261.9 ± 10.5 μM for a treatment period of 48 hr. The mRNA levels of the genes related to cell proliferation, Ki67, PCNA, and FoxM1, were reduced. Enterolactone induced accumulation of cells in the S phase, and a lower expression of Cyclin E1, Cyclin A2, Cyclin B1, and Cyclin B2 genes. There were almost no changes in the transcription levels of the genes that participate in G0/G1 phase regulation, CDK4, CDK6, and Cyclin D1. Furthermore, enterolactone interfered with the cytoskeleton by downregulating phosphorylation of the FAK/paxillin pathway, inhibiting migration and invasion of cells. The results suggest that enterolactone exerts an antitumor effect by regulating the expression of genes associated with cell proliferation and the cell cycle and by blocking the FAK/paxillin signaling pathway. These findings provide new insights into the molecular mechanisms behind the antitumor effect of enterolactone.

Granulocyte-colony-stimulating factor (G-cSF) is a member of the hematopoietic growth factor family that primarily affects the neutrophil lineage. G-cSF serves as a powerful mobilizer of peripheral blood stem cells and recombinant human G-cSF (rhG-cSF) has been used to treat granulocytopenia and neutropenia after chemotherapy for cancer patients. However, recent studies have found that G-cSF plays an important role in cancer progression. G-cSF expression is increased in different types of cancer cells, such as lung cancer, gastric cancer, colorectal cancer, invasive bladder carcinoma, glioma and breast cancer. However, it is unclear whether treatment with G-cSF has an adverse effect. The current review provides an overview of G-cSF in malignant breast cancer development and the data presented in this review are expected to provide new ideas for cancer therapy. Contents 1. introduction 2. Structure of the G-cSF gene 3. regulation of G-cSF gene expression 4. The G-cSF receptor 5. G-cSF expression in breast cancer 6. direct effects of G-cSF on breast cancer 7. role of tumor microenvironment in the effect of G-cSF on breast cancer 8. conclusions

CXXC5 is a member of the CXXC‐type zinc‐finger protein family. Proteins in this family play a pivotal role in epigenetic regulation by binding to unmethylated CpG islands in gene promoters through their characteristic CXXC domain. CXXC5 is a short protein (322 amino acids in length) that does not have any catalytic domain, but is able to bind to DNA and act as a transcription factor and epigenetic factor through protein‐protein interactions. Intriguingly, increasing evidence indicates that expression of the CXXC5 gene is controlled by multiple signaling pathways and a variety of transcription factors, positioning CXXC5 as an important signal integrator. In addition, CXXC5 is capable of regulating various signal transduction processes, including the TGF‐β, Wnt and ATM‐p53 pathways, thereby acting as a novel and crucial signaling coordinator. CXXC5 plays an important role in embryonic development and adult tissue homeostasis by regulating cell proliferation, differentiation and apoptosis. In keeping with these functions, aberrant expression or altered activity of CXXC5 has been shown to be involved in several human diseases including tumourigenesis. This review summarizes the current understanding of CXXC5 as a transcription factor and signaling regulator and coordinator.

Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression, yet the underlying mechanisms and functional mediators remain elusive. We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes (CAAs) in vitro. The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing. One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor (G-CSF). Recombinant human G-CSF treatment or stably expression of human G-CSF in triple-negative breast cancer (TNBC) cell lines enhanced EMT, migration, and invasion of cancer cells, by activating Stat3. Accordantly, targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody, a chemical inhibitor, or siRNAs for Stat3 could abrogate CAAs- or G-CSF-induced migration and invasion of breast cancer cells. The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells. Furthermore, in human breast cancer tissues, elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells. Together, our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAAs-derived G-CSF.

The increased atmospheric temperatures resulting from the increased concentration of atmospheric carbon dioxide (CO2) have had a profound influence on global rice production. China serves as an important area for producing and consuming rice. Therefore, exploring the effects of the simultaneously rising levels of atmospheric CO2 and temperatures on rice growth and quality in the future is very important. The present study was designed to measure the most important aspects of variation for rice-related physiological, ecological and quality indices in different growing periods under a simultaneous increase of CO2 and temperature, through simulation experiments in climate-controlled growth chambers, with southern rice as the study object. The results indicated that the ecological indices, rice phenology, and leaf area would decrease under a simultaneous increase of CO2 and temperature. For the physiological indices, Malondialdehyde (MDA) levels increased significantly in the seedling period. However, it showed the trend of increase and subsequent decrease in the heading and filling periods. In addition, the decomposition of soluble protein (SP) and soluble sugar (SS) accelerated in filling period. The rice quality index of the Head Rice Rate showed the decreasing trend and subsequent increase, but the Chalky Rice Rate and Protein Content indices gradually decreased while the Gel Consistency gradually increased.

Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233–620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer.