The role of TGF-β/SMAD4 signaling in cancer Zhao, Ming; Mishra, Lopa; Deng, Chu-Xia
International journal of biological sciences,
01/2018, Letnik:
14, Številka:
2
Journal Article
Recenzirano
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Transforming growth factor β (TGF-β) signaling pathway plays important roles in many biological processes, including cell growth, differentiation, apoptosis, migration, as well as cancer initiation ...and progression. SMAD4, which serves as the central mediator of TGF-β signaling, is specifically inactivated in over half of pancreatic duct adenocarcinoma, and varying degrees in many other types of cancers. In the past two decades, multiple studies have revealed that SMAD4 loss on its own does not initiate tumor formation, but can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic duct adenocarcinoma and APC inactivation in colorectal cancer. In other cases, such as skin cancer, loss of SMAD4 plays an important initiating role by disrupting DNA damage response and repair mechanisms and enhance genomic instability, suggesting its distinct roles in different types of tumors. This review lists SMAD4 mutations in various types of cancer and summarizes recent advances on SMAD4 with focuses on the function, signaling pathway, and the possibility of SMAD4 as a prognostic indicator.
The cellular environment where tumor cells reside is called the tumor microenvironment (TME), which consists of borders, blood vessels, lymph vessels, extracellular matrix (ECM), stromal cells, ...immune/inflammatory cells, secreted proteins, RNAs and small organelles. By dynamically interacting with tumor cells, stromal cells participate in all stages of tumor initiation, progression, metastasis, recurrence and drug response, and consequently, affect the fate of patients. During the processes of tumor evolution and metastasis initiation, stromal cells in TME also experience some changes and play roles in both the suppression and promotion of metastasis, while the overall function of stromal cells is beneficial for cancer cell survival and movement. In this review, we examine the effects of stromal cells in TME on metastasis initiation, including angiogenesis, epithelial-mesenchymal transition (EMT) and invasion. We also highlight functions of proteins, RNAs and small organelles secreted by stromal cells in their influences on multiple stages of tumor metastasis.
COVID-19 patients exhibit flu-like symptoms, such as persistent coughing, fever, shortness of breath, and difficulty breathing, which are similar to the Severe Acute Respiratory Syndrome (SARS), and ...the Middle East Respiratory Syndrome (MERS). Because SARS-CoV-2 is a new pathogen, people of all ages have no immunity to it and generally susceptible to infection. The war against COVID-19 will continue on a global scale. ...the knowledge the virus, the mechanism of its infection, the characteristics of the epidemic transmission are essentially important for effective fighting against this deadly disease. Lo et al. reported their experience on the evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical features of all 10 patients in Macau, and recommended the assessment of both fecal and respiratory specimens for enhancing diagnostic sensitivity 3. Because of no specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease, many drugs have been used in the therapy. ...we bring up a comprehensive review on what we have learned and to be learned by Li et al, who cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease in comparison with SARS and MERS 11.
Cancer related exosomes are nano-size membrane vesicles that play important roles in tumor microenvironment. Emerging evidence indicates that exosomes can load unique cargoes, including proteins and ...nucleic acids that reflect the condition of tumor. Therefore, exosomes are being used as diagnostic and prognostic biomarkers for various cancers. In this review, we describe the current progresses of cancer related exosomes, including their biogenesis, molecular contents, biological functions, sources where they are derived from, and methods for their detection. We will also discuss the current exosomal biomarkers and the utilization of them for early diagnosis and prognostics in cancer.
The sirtuins are a highly conserved family of NAD+-dependent enzymes that regulate lifespan in lower organisms. Recently, the mammalian sirtuins have been connected to an ever widening circle of ...activities that encompass cellular stress resistance, genomic stability, tumorigenesis and energy metabolism. Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live.
Steroid receptor coactivator-3 (SRC-3), also known as amplified in breast cancer 1 (AIB1), is a member of the SRC family. SRC-3 regulates not only the transcriptional activity of nuclear receptors ...but also many other transcription factors. Besides the essential role of SRC-3 in physiological functions, it also acts as an oncogene to promote multiple aspects of cancer. This review updates the important progress of SRC-3 in carcinogenesis and summarizes its mode of action, which provides clues for cancer therapy.
SIRT1 has been considered as a tumor promoter because of its increased expression in some types of cancers and its role in inactivating proteins that are involved in tumor suppression and DNA damage ...repair. However, recent studies demonstrated that SIRT1 levels are reduced in some other types of cancers, and that SIRT1 deficiency results in genetic instability and tumorigenesis, while overexpression of SIRT1 attenuates cancer formation in mice heterozygous for tumor suppressor p53 or APC. Here, I review these recent findings and discuss the possibility that activation of SIRT1 both extends lifespan and inhibits cancer formation.
Efficient red emissive carbon dots (CDs) in aqueous solutions are very scarce for high performance bioimaging applications. In this work, we report a one-step solvothermal treatment to synthesize ...pure red emissive CDs (FA-CDs) from citric acid and urea in formic acid without complicated purification procedures. Photoluminescence quantum yield (PLQY) of 43.4% was observed in their dimethyl sulfoxide solutions. High PLQY up to 21.9% in aqueous solutions was achieved in their bovine serum albumin (BSA) composites (FA-CDs@BSA) with significantly enhanced multi-photon fluorescence. The strong surface electron-withdrawing structure of FA-CDs caused by the high content of C = O groups contributes for their pure red emission. Owing to the significantly enhanced single and multi-photon red fluorescence and enlarged particle sizes after composing with BSA, in vivo tumor imaging and two-photon fluorescence imaging of blood vessels in mouse ear have been realized via intravenous injection of FA-CDs@BSA aqueous solutions.
Tumor heterogeneity is one of the hallmarks of cancer and a challenge in the field of oncology. Tumor heterogeneity is the main cause of drug resistance, leading to therapeutic failure. Mechanically, ...tumor heterogeneity either directly affects therapeutic targets or shapes the tumor microenvironment (TME) by defining transcriptomic and phenotypic profiles to influence drug resistance. Tumor heterogeneity evolves spatially and temporally during tumor development, leading to the constant reprogramming of the TME. Advances in molecular profiling technologies and precision oncology platforms have allowed us to uncover the impact of tumor heterogeneity on drug resistance in the context of the TME. In this review, we focus on the processes during which genomic mutations drive tumor heterogeneity and the mechanisms through which tumor heterogeneity reprograms the TME to affect drug resistance and patient prognosis.
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