Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
183
result(s) for
"Liu, Suling"
Sort by:
Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis
Cancer cells display phenotypic equilibrium between the stem-like and differentiated states during neoplastic homeostasis. The functional and mechanistic implications of this subpopulation plasticity remain largely unknown. Herein, it is demonstrated that the breast cancer stem cell (BCSC) secretome autonomously compresses the stem cell population. Co-implantation with BCSCs decreases the tumor-initiating capacity yet increases metastasis of accompanying cancer cells, wherein DKK1 is identified as a pivotal factor secreted by BCSCs for such functions. DKK1-promotes differentiation is indispensable for disseminated tumor cell metastatic outgrowth. In contrast, DKK1 inhibitors substantially relieve the metastatic burden by restraining metastatic cells in the dormant state. DKK1 increases the expression of SLC7A11 to protect metastasizing cancer cells from lipid peroxidation and ferroptosis. Combined treatment with a ferroptosis inducer and a DKK1 inhibitor exhibits synergistic effects in diminishing metastasis. Hence, this study deciphers the contribution of CSC-regulated phenotypic plasticity in metastatic colonization and provides therapeutic approaches to limit metastatic outgrowth.
The contribution of breast cancer stem cells (BCSCs) to metastasis needs further elucidation. Here, the authors show that BCSCs secrete DKK1 to protect metastasizing cancer cells from ferroptosis via upregulation of SLC7A11, and further show that the combination of a ferroptosis inducer with a DKK1 inhibitor reduces metastasis.
Journal Article
Breast cancer stem cells, cytokine networks, and the tumor microenvironment
Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment - including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells - through networks of cytokines and growth factors. Since these components have a direct influence on CSC properties, they represent attractive targets for therapeutic development.
Journal Article
TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer
Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ERα trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously.
Vasculogenic mimicry (VM) contributes to the development of triple-negative breast cancer. In this study, the authors show that TEM8 is expressed in VM-forming breast cancer stem cells and it promotes stemness and VM differentiation capacity through a RhoC/ROCK1/SMAD5 axis
Journal Article
Molecular mechanisms and clinical studies of iguratimod for the treatment of ankylosing spondylitis
Iguratimod (IGU) is a novel small molecule anti-rheumatic drug with the effect of non-steroidal anti-inflammatory drug and disease-modifying anti-rheumatic drug. IGU has various mechanisms of action, including inhibition of prostaglandin E2, tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17) production, inhibition of macrophage migration inhibitory factor (MIF)-induced proinflammatory effects, inhibition of osteoclastogenesis, and promotion of osteoblastic differentiation. Ankylosing spondylitis (AS) is the major subtype of spondyloarthritis that affects the axial skeleton, causing inflammatory back pain, which can lead to impairments in structure and function and a decrease in quality of life. Theories on pathogenesis of AS include misfolding of human leukocyte antigen-B27 during its assembly leading to endoplasmic reticulum stress and unfolded protein response (UPR). Activation of UPR genes results in release of TNF-α and IL-17, which have been shown to be important in the development of AS. In addition, current evidence suggests the importance of cyclooxygenase-2/prostaglandin E2 pathway and MIF in the pathogenesis of AS. Current drugs for the treatment of AS are limited and exploration of effective drugs is needed. IGU may be effective for the treatment of AS given that its mechanisms of action are closely related to the pathogenesis of AS. In fact, several small-scale clinical trials have shown the efficacy of IGU for the treatment of AS. This article reviews the molecular mechanisms of IGU that are related to the pathogenesis of AS and clinical trials of IGU for the treatment of AS, providing a reference for future clinical application of IGU for AS.
Journal Article
Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets
The family of aldehyde dehydrogenases (ALDHs) contains 19 isozymes and is involved in the oxidation of endogenous and exogenous aldehydes to carboxylic acids, which contributes to cellular and tissue homeostasis. ALDHs play essential parts in detoxification, biosynthesis, and antioxidants, which are of important value for cell proliferation, differentiation, and survival in normal body tissues. However, ALDHs are frequently dysregulated and associated with various diseases like Alzheimer's disease, Parkinson's disease, and especially solid tumors. Notably, the involvement of the ALDHs in tumor progression is responsible for the maintenance of the stem‐cell‐like phenotype, triggering rapid and aggressive clinical progressions. ALDHs have captured increasing attention as biomarkers for disease diagnosis and prognosis. Nevertheless, these require further longitudinal clinical studies in large populations for broad application. This review summarizes our current knowledge regarding ALDHs as potential biomarkers in tumors and several non‐tumor diseases, as well as recent advances in our understanding of the functions and underlying molecular mechanisms of ALDHs in disease development. Finally, we discuss the therapeutic potential of ALDHs in diseases, especially in tumor therapy with an emphasis on their clinical implications. The human aldehyde dehydrogenase (ALDH) superfamily comprises 19 isozymes and can be divided into 11 distinct families. ALDHs are a group of nicotinamide adenine dinucleotide phosphate (NADP+)‐dependent enzymes that could catalyze the reversible oxidation of endogenous and exogenous aldehydes to their corresponding carboxylic acids. However, ALDHs are frequently dysregulated and associated with various diseases like Alzheimer's disease, Parkinson's disease, and especially solid tumors. Different ALDH isoenzymes are believed to be potential biomarkers or therapeutic targets in different diseases.
Journal Article
Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance
Chemotherapy and radiation not only trigger cancer cell apoptosis but also damage stromal cells in the tumour microenvironment (TME), inducing a senescence-associated secretory phenotype (SASP) characterized by chronic secretion of diverse soluble factors. Here we report serine protease inhibitor Kazal type I (SPINK1), a SASP factor produced in human stromal cells after genotoxic treatment. DNA damage causes SPINK1 expression by engaging NF-κB and C/EBP, while paracrine SPINK1 promotes cancer cell aggressiveness particularly chemoresistance. Strikingly, SPINK1 reprograms the expression profile of cancer cells, causing prominent epithelial-endothelial transition (EET), a phenotypic switch mediated by EGFR signaling but hitherto rarely reported for a SASP factor. In vivo, SPINK1 is expressed in the stroma of solid tumours and is routinely detectable in peripheral blood of cancer patients after chemotherapy. Our study substantiates SPINK1 as both a targetable SASP factor and a novel noninvasive biomarker of therapeutically damaged TME for disease control and clinical surveillance.
Tumour microenvironment actively contributes to drug resistance in clinical oncology. Here, the authors show that genotoxic stress induces senescence in human stromal cells, which in turn secrete serine protease inhibitor Kazal type 1 (SPINK1) and promote acquired resistance of cancer cells via EGFR-mediated paracrine signaling.
Journal Article
Myeloid PTEN promotes chemotherapy-induced NLRP3-inflammasome activation and antitumour immunity
PTEN is a dual-specificity phosphatase that is frequently mutated in human cancer, and its deficiency in cancer has been associated with therapy resistance and poor survival. Although the intrinsic tumour-suppressor function of PTEN has been well established, evidence of its role in the tumour immune microenvironment is lacking. Here, we show that chemotherapy-induced antitumour immune responses and tumour suppression rely on myeloid-cell PTEN, which is essential for chemotherapy-induced activation of the NLRP3 inflammasome and antitumour immunity. PTEN directly interacts with and dephosphorylates NLRP3 to enable NLRP3–ASC interaction, inflammasome assembly and activation. Importantly, supplementation of IL-1β restores chemotherapy sensitivity in mouse myeloid cells with a PTEN deficiency. Clinically, chemotherapy-induced IL-1β production and antitumour immunity in patients with cancer is correlated with PTEN expression in myeloid cells, but not tumour cells. Our results demonstrate that myeloid PTEN can determine chemotherapy responsiveness by promoting NLRP3-dependent antitumour immunity and suggest that myeloid PTEN might be a potential biomarker to predict chemotherapy responses.Huang et al. show that, in response to chemotherapy, PTEN directly interacts with NLRP3 in myeloid cells to enhance inflammasome activation and antitumour immune responses.
Journal Article
Identification of cancer-type specific expression patterns for active aldehyde dehydrogenase (ALDH) isoforms in ALDEFLUOR assay
Aldehyde dehydrogenases (ALDHs) defend intracellular homeostasis by catalyzing the conversion of toxic aldehydes into non-toxic carboxylic acids, which is of particular importance to the self-renewal of stem cells and cancer stem cells. The widely used ALDEFLUOR assay was initially designed to indicate the activity of ALDH1A1 in leukemia and has been demonstrated to detect the enzyme activity of several other ALDH isoforms in various cancer types in recent years. However, it is still elusive which isoforms, among the 19 ALDH isoforms in human genome, are the potential contributors in catalyzing ALDEFLUOR assay in different cancers. In the current study, we performed a screening via overexpressing each ALDH isoform to assess their ability of catalyzing ALDEFLUOR assay. Our results demonstrate that nine isoforms are active in ALDEFLUOR assay, whose overexpression significantly increases ALDH-positive (ALDH+) population. Further analysis of the expression of these active isoforms in various cancers reveals cancer-type specific expression patterns, suggesting that different cancer types may exhibit ALDEFLUOR activity through expression of specific active ALDH isoforms. This study strongly indicates that a detailed elucidation of the functions for each active ALDH isoform in CSCs is necessary and important for a profound understanding of the underlying mechanisms of ALDH-associated stemness.
Journal Article
Cancer Stem Cells and Neovascularization
Cancer stem cells (CSCs) refer to a subpopulation of cancer cells responsible for tumorigenesis, metastasis, and drug resistance. Increasing evidence suggests that CSC-associated tumor neovascularization partially contributes to the failure of cancer treatment. In this review, we discuss the roles of CSCs on tumor-associated angiogenesis via trans-differentiation or forming the capillary-like vasculogenic mimicry, as well as the roles of CSCs on facilitating endothelial cell-involved angiogenesis to support tumor progression and metastasis. Furthermore, we discuss the underlying regulation mechanisms, including the intrinsic signals of CSCs and the extrinsic signals such as cytokines from the tumor microenvironment. Further research is required to identify and verify some novel targets to develop efficient therapeutic approaches for more efficient cancer treatment through interfering CSC-mediated neovascularization.
Journal Article