Targeted Delivery of Natural Bioactives and Lipid-nanocargos against Signaling Pathways Involved in Skin Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Mohammad Kashif Iqubal ◽  
Aiswarya Chaudhuri ◽  
Ashif Iqubal ◽  
Sadaf Saleem ◽  
Madan Mohan Gupta ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Targeted Delivery ◽  
Skin Pigmentation ◽  
Wnt Signaling Pathway ◽  
Human Beings ◽  
Radiation Chemical ◽  
Cell Leukemia Virus Type ◽  
Human T Cell

: At present, skin cancer is a widespread malignancy in human beings. Among diverse population types, Caucasian populations are much more prone in comparison to darker skin populations due to the comparative lack of skin pigmentation. Skin cancer is divided into malignant and non-melanoma skin cancer, which is additionally categorized as basal and squamous cell carcinoma. The exposure to ultraviolet radiation, chemical carcinogen (polycyclic aromatic hydrocarbons, arsenic, tar, etc.), and viruses (herpes virus, human papillomavirus, and human T-cell leukemia virus type-1) are major contributing factors of skin cancer. There are distinct pathways available through which skin cancer develops, such as the JAKSTAT pathway, Akt pathway, MAPKs signaling pathway, Wnt signaling pathway, to name a few. Currently, several targeted treatments are available, such as monoclonal antibodies, which have dramatically changed the line of treatment of this disease but possess major therapeutic limitations. Thus, recently many phytochemicals have been evaluated either alone or in combination with the existing synthetic drugs to overcome their limitations and have found to play a promising role in the prevention and treatment. In this review, complete tracery of skin cancer, starting from the signaling pathways involved, newer developed drugs with their targets and limitations along with the emerging role of natural products alone or in combination as potent anticancer agents and their molecular mechanism involved has been discussed. Apart from this, various nanocargos have also been mentioned here, which can play a significant role in the management and treatment of different types of skin cancer.

scholarly journals Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Garima Sharma ◽  
Ashish Ranjan Sharma ◽  
Eun-Min Seo ◽  
Ju-Suk Nam
Keyword(s):  
Genetic Polymorphism ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
The Other ◽  
Present Review ◽  
Receptor Complex ◽  
Related Proteins ◽  
Related Association

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

scholarly journals Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin

2019 ◽  
Vol 20 (21) ◽  
pp. 5391 ◽  
Author(s):  
Wörthmüller ◽  
Salicio ◽  
Oberson ◽  
Blum ◽  
Schwaller
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Expression System ◽  
Single Agent ◽  
Wnt Signaling Pathway ◽  
Tumor Formation ◽  
Mesenchymal Transition

Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca2+-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells’ growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.

scholarly journals Autophagy Is Required for Hepatic Differentiation of Hepatic Progenitor Cells via Wnt Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jianxing Zeng ◽  
Yingying Jing ◽  
Qionglan Wu ◽  
Jinhua Zeng ◽  
Lixin Wei ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Hepatic Progenitor Cells ◽  
Hepatic Differentiation ◽  
Development And Differentiation ◽  
Progenitor Cell Line

The molecular mechanisms regulating differentiation of hepatic progenitor cells (HPCs), which play pivotal roles in liver regeneration and development, remain obscure. Autophagy and Wnt signaling pathways regulate the development and differentiation of stem cells in various organs. However, the roles of autophagy and Wnt signaling pathways in hepatic differentiation of HPCs are not well understood. Here, we describe the effects of autophagy and Wnt signaling pathways during hepatic differentiation of HPCs. We used a well-established rat hepatic progenitor cell line called WB-F344, which was treated with differentiation medium to promote differentiation of WB-F344 cells along the hepatic phenotype. Firstly, autophagy was highly activated in HPCs and gradually decreased during hepatic differentiation of HPCs. Induction of autophagy by rapamycin or starvation suppressed hepatic differentiation of HPCs. Secondly, Wnt3a signaling pathway was downregulated, and Wnt5a signaling pathway was upregulated in hepatic differentiation of HPCs. At last, Wnt3a signaling pathway was enhanced, and Wnt5a signaling pathway was inhibited by activation of autophagy during hepatic differentiation of HPCs. In summary, these results demonstrate that autophagy regulates hepatic differentiation of hepatic progenitor cells through Wnt signaling pathway.

scholarly journals Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1α Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Zhen Tan ◽  
Baochun Zhou ◽  
Jianrui Zheng ◽  
Yongcan Huang ◽  
Hui Zeng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Bioactive Scaffolds ◽  
Marrow Mesenchymal Stem Cells ◽  
Angiogenesis Process ◽  
Canonical Wnt

The combination of osteogenesis and angiogenesis dual-delivery trace element-carrying bioactive scaffolds and stem cells is a promising method for bone regeneration and repair. Canonical Wnt and HIF-1α signaling pathways are vital for BMSCs’ osteogenic differentiation and secretion of osteogenic factors, respectively. Simultaneously, lithium (Li) and copper (Cu) can activate the canonical Wnt and HIF-1α signaling pathway, respectively. Moreover, emerging evidence has shown that the canonical Wnt and HIF signaling pathways are related to coupling osteogenesis and angiogenesis. However, it is still unclear whether the lithium- and copper-doped bioactive scaffold can induce the coupling of the osteogenesis and angiogenesis in BMSCs and the underlying mechanism. So, we fabricated a lithium- (Li+-) and copper- (Cu2+-) doped organic/inorganic (Li 2.5-Cu 1.0-HA/Col) scaffold to evaluate the coupling osteogenesis and angiogenesis effects of lithium and copper on BMSCs and further explore its mechanism. We investigated that the sustained release of lithium and copper from the Li 2.5-Cu 1.0-HA/Col scaffold could couple the osteogenesis- and angiogenesis-related factor secretion in BMSCs seeding on it. Moreover, our results showed that 500 μM Li+ could activate the canonical Wnt signaling pathway and rescue the XAV-939 inhibition on it. In addition, we demonstrated that the 25 μM Cu2+ was similar to 1% oxygen environment in terms of the effectiveness of activating the HIF-1α signaling pathway. More importantly, the combination stimuli of Li+ and Cu2+ could couple the osteogenesis and angiogenesis process and further upregulate the osteogenesis- and angiogenesis-related gene expression via crosstalk between the canonical Wnt and HIF-1α signaling pathway. In conclusion, this study revealed that lithium and copper could crosstalk between the canonical Wnt and HIF-1α signaling pathways to couple the osteogenesis and angiogenesis in BMSCs when they are sustainably released from the Li-Cu-HA/Col scaffold.

scholarly journals Study of APOBEC3B focused breast cancer pathways and the clinical relevance

2021 ◽  
Author(s):  
Hani Choudhary ◽  
Ashwag Albukhari ◽  
Mohammad Mobashir ◽  
Wesam Abdulaal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Signaling Pathways ◽  
Clinical Relevance ◽  
Survival Curve ◽  
Immune Signaling ◽  
Systematic Analysis ◽  
Cell Leukemia Virus Type ◽  
P53 Signaling ◽  
Human T Cell

Abstract APOBEC3B is considered as an enzymatic source of mutation in case of breast cancer and Human T-Cell Leukemia Virus Type 1 and Bone Leiomyosarcoma are also associated with it. The major functions controlled or affected due to APOBEC3B are gene expression, mRNA editing such as C -> U conversion, and deoxycytidine deaminase activity. Here, the main goal of the study was to perform a systematic analysis of APOBEC3B associated genes and its functional impact in human breast cancer. For this purpose, the datasets have been utilized from the publicly available database such as GEO, OncoLnc, and TCGA. Based on the requirements for fetching the values, different bioinformatics approaches have been applied at different levels. Further, co-regulated genes obtained from co-expression network have been processed and the mutated genes with the pathways enrichment analysis, and the clinical relevance using survival curve analysis by using OncoLnc have been performed. In the results, we found that there are a number of critical pathways known to directly associated with breast cancer are altered because of the genes which are either overexpressed or top mutated and are associated with APOBEC3B and these pathways are cell cycle, p53 signaling, immune signaling pathways, progesterone-mediated oocyte maturation, apoptosis, critical metabolic pathways, and pathways in cancers. From the mutational and survival analysis data, we also observe that there are a number of well-known cancer associated signaling pathways (mainly cancer), immune signaling pathway, critical metabolic associated pathways, cell cycle, ubiquitin-proteasomal signaling pathways, and p53 signaling. Network-level study of pathways and their components CD40LG as the potential gene where CD40LG is directly affecting 10 pathways and most of them are the parts of immune system and known to control a number of leading human diseases including cancers.

scholarly journals In Vivo Analysis of Wnt Signaling in Bone

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2630-2634 ◽  
Author(s):  
Donald A. Glass ◽  
Gerard Karsenty
Keyword(s):  
Bone Mass ◽  
Wnt Signaling ◽  
Bone Remodeling ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Osteoclast Differentiation ◽  
Wnt Signaling Pathway ◽  
Human Beings ◽  
High Bone Mass ◽  
High Bone

Bone remodeling requires osteoblasts and osteoclasts working in concert to maintain a constant bone mass. The dysregulation of signaling pathways that affect osteoblast or osteoclast differentiation or function leads to either osteopenia or high bone mass. The discovery that activating and inactivating mutations in low-density lipoprotein receptor-related protein 5, a putative Wnt coreceptor, led to high bone mass and low bone mass in human beings, respectively, generated a tremendous amount of interest in the possible role of the Wnt signaling pathway in the regulation of bone remodeling. A number of mouse models have been generated to study a collection of Wnt signaling molecules that have been identified as regulators of bone mass. These mouse models help establish the canonical Wnt signaling pathway as a major regulator of chondrogenesis, osteoblastogenesis, and osteoclastogenesis. This review will summarize these advances.

scholarly journals Novel newt regeneration genes regulate Wingless signaling to restore patterning in Drosophila eye

2021 ◽  
Author(s):  
Abijeet Singh Mehta ◽  
Prajakta Deshpande ◽  
Anuradha Venkatakrishnan Chimata ◽  
Panagiotis A. Tsonis ◽  
Amit Singh
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Ectopic Expression ◽  
Wnt Signaling Pathway ◽  
Protein S ◽  
Photoreceptor Cells ◽  
Body Parts ◽  
Regeneration Potential ◽  
Regeneration Capability

AbstractA fundamental process of regeneration, which varies among animals, recruits conserved signaling pathways to restore missing parts. Only a few animals like newts can repeatedly regenerate lost body parts throughout their lifespan that can be attributed to strategic regulation of conserved signaling pathways by newt’s regeneration tool-kit genes. Here we report the use of a genetically tractable Drosophila eye model to demonstrate the regeneration potential of a group of unique protein(s) from newt (Notophthalmus viridescens), which when ectopically expressed can significantly rescue missing photoreceptor cells in a Drosophila eye mutant. These newt proteins with signal peptides motifs exhibit non-cell-autonomous rescue properties and their regeneration potential even extends into later stages of fly development. Ectopic expression of these newt genes can rescue eye mutant phenotype by promoting cell proliferation and blocking cell death. These novel newt genes downregulate the evolutionarily conserved Wingless (Wg)/Wnt signaling pathway to promote rescue. Modulation of Wg/Wnt signaling levels by using antagonists or agonists of Wg/Wnt signaling pathway in eye mutant background where newt gene(s) is ectopically expressed suggests that Wg signaling acts downstream of newt genes. Our data highlights the regeneration potential of novel newt proteins that regulate conserved pathways to trigger a robust regeneration response in Drosophila model with weak regeneration capability.

scholarly journals Activation of the Hedgehog and Wnt/β-Catenin Signaling Pathways in Basal Cell Carcinoma

2021 ◽  
pp. 506-512
Author(s):  
Tomoaki Takada
Keyword(s):  
Basal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Basal Cell ◽  
Transcriptional Activation ◽  
Wnt Signaling Pathway ◽  
Downstream Effectors ◽  
Mrna Binding

In basal cell carcinoma (BCC) tumorigenesis, interaction between Hedgehog (Hh) and Wnt/β-catenin (Wnt) signaling pathways has been investigated, but not completely elucidated. Here, a case of sporadic BCC in an 80-year-old man is presented, and the effectiveness of SMO inhibitors in case of relapse is predicted. The aim of this study was to determine whether the SMO inhibitors can be effective in treating this individual should the tumor recur in the future. Immunohistochemistry (IHC) was performed in a tumor and the adjacent skin tissue from the patient. IHC within the same BCC tissue specimen revealed that Glioma-associated oncogene 1 (GLI1) and Smoothened (SMO) in the Hh signaling pathway and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in the Wnt signaling pathway were overexpressed. Hh and Wnt signaling pathways were activated. These findings suggest that the patient might be resistant to treatment with SMO inhibitors because of the interaction between Hh and Wnt signaling pathways. Overexpression of GLI1 leads to transcriptional activation, making it an attractive molecular target for anticancer therapy owing to the downstream effectors of the cascade.

scholarly journals Mesenchymal stromal cells induce inhibitory effects on hepatocellular carcinoma through various signaling pathways

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jafar Ai ◽  
Neda Ketabchi ◽  
Javad Verdi ◽  
Nematollah Gheibi ◽  
Hossein Khadem Haghighian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wnt Signaling Pathway ◽  
Trophic Factors ◽  
Limited Information ◽  
Inhibitory Effects

AbstractHepatocellular carcinoma (HCC) is the most prevalent type of malignant liver disease worldwide. Molecular changes in HCC collectively contribute to Wnt/β-catenin, as a tumor proliferative signaling pathway, toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB), as well as the c-Jun NH2-terminal kinase (JNK), predominant signaling pathways linked to the release of tumor-promoting cytokines. It should also be noted that the Hippo signaling pathway plays an important role in organ size control, particularly in promoting tumorigenesis and HCC development. Nowadays, mesenchymal stromal cells (MSCs)-based therapies have been the subject of in vitro, in vivo, and clinical studies for liver such as cirrhosis, liver failure, and HCC. At present, despite the importance of basic molecular pathways of malignancies, limited information has been obtained on this background. Therefore, it can be difficult to determine the true concept of interactions between MSCs and tumor cells. What is known, these cells could migrate toward tumor sites so apply effects via paracrine interaction on HCC cells. For example, one of the inhibitory effects of MSCs is the overexpression of dickkopf-related protein 1 (DKK-1) as an important antagonist of the Wnt signaling pathway. A growing body of research challenging the therapeutic roles of MSCs through the secretion of various trophic factors in HCC. This review illustrates the complex behavior of MSCs and precisely how their inhibitory signals interface with HCC tumor cells.

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