Cellular Oncology, Год журнала: 2021, Номер 44(3), С. 473 - 494
Опубликована: Март 11, 2021
Язык: Английский
Experimental & Molecular Medicine, Год журнала: 2020, Номер 52(2), С. 183 - 191
Опубликована: Фев. 1, 2020
Abstract Wnt/β-catenin signaling is implicated in many physiological processes, including development, tissue homeostasis, and regeneration. In human cancers, highly activated, which has led to the development of various Wnt inhibitors for cancer therapies. Nonetheless, blockade causes side effects such as impairment homeostasis Recently, several studies have identified cancer-specific regulators. this review, we discuss currently being used clinical trials suggest how additional regulators could be utilized treat signaling-associated cancer.
Язык: Английский
Процитировано
372
The EMBO Journal, Год журнала: 2020, Номер 39(19)
Опубликована: Авг. 13, 2020
Язык: Английский
Процитировано
348
Cells, Год журнала: 2019, Номер 8(8), С. 826 - 826
Опубликована: Авг. 3, 2019
Developmental signaling pathways control a vast array of biological processes during embryogenesis and in adult life. The WNT pathway was discovered simultaneously cancer development. Recent advances have expanded the role to wide range pathologies humans. Here, we discuss its human disease some WNT-related treatments.
Язык: Английский
Процитировано
197
Cancers, Год журнала: 2019, Номер 11(7), С. 965 - 965
Опубликована: Июль 9, 2019
Triple-negative breast cancer (TNBC) is a highly aggressive form of that lacks targeted therapy options, and patients diagnosed with TNBC have poorer outcomes than other subtypes. Emerging evidence suggests stem cells (BCSCs), which tumor-initiating potential possess self-renewal capacity, may be responsible for this poor outcome by promoting resistance, metastasis, recurrence. been consistently reported to display cell (CSC) signatures at functional, molecular, transcriptional levels. In recent decades, CSC-targeting strategies shown therapeutic effects on in multiple preclinical studies, some these are currently being evaluated clinical trials. Therefore, understanding CSC biology has the guide discovery novel agents future. review, we focus signaling pathways (SRSPs) aberrantly activated discuss specific components involved cells. Additionally, describe molecular mechanisms shared both CSCs, including metabolic plasticity, enables switch between according substrate availability meet energetic biosynthetic demands rapid growth survival under harsh conditions. We highlight CSCs as key regulators driving aggressiveness TNBC. Thus, manipulation can strategy
Язык: Английский
Процитировано
152
Molecular Therapy, Год журнала: 2020, Номер 29(3), С. 1258 - 1278
Опубликована: Окт. 15, 2020
Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cell survival. The present study aimed to investigate regulatory role lncRNA small nucleolar host gene 11 (SNHG11) GC. We show that SNHG11 upregulated GC, and its upregulation correlated with dismal patient outcomes. Functionally, aggravated oncogenic facilitate proliferation, stemness, migration, invasion, epithelial-to-mesenchymal transition (EMT) Mechanistically, post-transcriptionally catenin beta 1 (CTNNB1) related 12 (ATG12) through miR-483-3p/miR-1276, while processing precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. induced GSK-3β ubiquitination interacting Cullin 4A (CUL4A) further activate Wnt/β-catenin pathway. Intriguingly, regulated a manner dependent on ATG12 rather than pathway, whereas contributed malignant behaviors GC cells via both pathways. Finally, shown be transcriptionally TCF7L2. In conclusion, we reveal an onco-lncRNA might promising prognostic therapeutic target
Язык: Английский
Процитировано
151
Genes & Diseases, Год журнала: 2023, Номер 11(1), С. 103 - 134
Опубликована: Март 24, 2023
Wnt signaling plays a major role in regulating cell proliferation and differentiation. The ligands are family of 19 secreted glycoproteins that mediate their effects via binding to Frizzled receptors LRP5/6 coreceptors transducing the signal either through β-catenin canonical pathway or series other proteins noncanonical pathway. Many individual components both have additional functions throughout body, establishing complex interplay between pathways. This crosstalk pathways gives vital many cellular organ processes. Dysregulation this system has been implicated diseases affecting wide array systems, including cancer embryological defects, can even cause embryonic lethality. complexity its interacting made target for therapeutic treatments. However, stimulatory inhibitory treatments come with potential risks need be addressed. review synthesized much current knowledge on pathway, beginning history signaling. It thoroughly described different variants signaling, canonical, Wnt/PCP, Wnt/Ca2+ Further description involved each involvement Finally, explained various processes
Язык: Английский
Процитировано
84
Genes & Diseases, Год журнала: 2023, Номер 11(3), С. 101026 - 101026
Опубликована: Июль 22, 2023
The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. proteins are secreted, lipid-modified molecules that activate the canonical (β-catenin dependent) non-canonical independent) pathways. Cellular behaviors such as proliferation, differentiation, maturation, proper body-axis specification carried out by pathway, which is best characterized of known paths. has emerged an important factor stem cell biology to affect self-renewal cells various tissues. This includes but not limited embryonic, hematopoietic, mesenchymal, gut, neural, epidermal cells. also been implicated tumor exhibit cell-like properties. crucial for bone formation presents potential target therapeutics disorders. Not surprisingly, aberrant associated with wide variety diseases, including cancer. Mutations members cancer can lead unchecked epithelial-mesenchymal transition, metastasis. Altogether, advances understanding dysregulated disease have paved way novel components pathway. Beginning brief overview mechanisms Wnt, this review aims summarize current knowledge cells, aberrations targeting preclinical clinical studies.
Язык: Английский
Процитировано
45
Journal of Experimental & Clinical Cancer Research, Год журнала: 2019, Номер 38(1)
Опубликована: Июль 12, 2019
The mechanism underlying breast cancer stem cell (BCSCs) characteristics remains to be fully elucidated. Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a pivotal role in regulating BCSCs stemness.LncRNA LUCAT1 expression was assessed tissues (n = 151 cases) by situ hybridization. Sphere-formation assay and colony formation were used detect self-renewal proliferation, respectively. RNA immunoprecipitation, pull down luciferase reporter assays identify TCF7L2 as the direct target of miR-5582-3p. activity Wnt/β-catenin pathway analyzed TOP/FOP-Flash assays, western blot immunohistochemistry (IHC).This study found related tumor size (p 0.015), lymph node metastasis 0.002) TNM staging < 0.001). High indicated shorter overall survival 0.006) disease-free 0.011). Furthermore, more expressed than cells (BCCs) lncRNA microarray chips. up-regulation promoted proliferation BCCs, while down-regulation inhibited BCSCs. MiR-5582-3p directly bound negatively regulated their expression. affected pathway.LUCAT1 might significant biomarker evaluate prognosis cancer. increased stem-like properties BCCs stemness competitively binding miR-5582-3p with enhancing pathway. LUCAT1/miR-5582-3p/TCF7L2 axis provides insights for regulatory stemness, new strategies clinical practice.
Язык: Английский
Процитировано
122
Genes, Год журнала: 2020, Номер 11(8), С. 886 - 886
Опубликована: Авг. 4, 2020
Wnt signaling is an evolutionarily conserved metazoan cell communication pathway required for proper animal development. Of the myriad of events that have been ascribed to cellular activation by ligands, canonical Wnt/β-catenin has most studied and best understood. Misregulation implicated in developmental defects embryo major diseases adult. Despite latter, no drugs inhibit approved FDA. In this review, we explore least understood step pathway—nuclear regulation target gene transcription. We initially describe our current understanding importation β-catenin into nucleus. then focus on mechanism action nuclear proteins driving Finally, concept a enhanceosome propose modified model describes necessary components transcription genes.
Язык: Английский
Процитировано
99
Cellular Physiology and Biochemistry, Год журнала: 2017, Номер 41(6), С. 2489 - 2502
Опубликована: Янв. 1, 2017
The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In present study, we investigated whether CRNDE was involved in development via binding microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) enhance Wnt signaling pathway.Quantitative polymerase chain reaction used detect CRNDE, miR-217 TCF7L2 tissues cells. CCK-8 assay, wound healing Transwell assay were cell proliferation, invasion, respectively. Western blotting luciferase activity assays identify as one direct targets miR-217. Wnt/β-catenin pathway analyzed by TOPflash subcellular localization β-catenin western confocal microscopy.In this found that high expression is negatively correlated low tissue dual reporter analysis showed bound regulate their expression. down-regulation inhibited invasion vitro vivo inhibitions both completely blocked after inhibition or overexpression. Finally, rescued over-expression. Consistently immunostaining b-catenin nucleus significantly decreased over-expression.The study suggest involves cells increasing through competitively.
Язык: Английский
Процитировано
90