Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway

Mt, Weng; Tsao, Po‐Nien; Lin, HL; Tung, CC; Yt, Chang; Jm, Wong; Sc, Wei

doi:10.1371/journal.pone.0144322

Cited by 44 publications

(37 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The proteolytic activity of metastatic tumor cells is their intrinsic feature, allowing them to transmigrate through the basal membrane and further, with invasion through the stroma [39]. Colorectal tumor progression was associated with overexpression of MMP-7 [40] and MMP-14, which is also known as a membrane type 1-matrix metalloproteinase (MT1-MMP) [39,41]. In the present paper we showed that SPF may decrease mRNA expression of MMP-7 and MT1-MMP.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA

et al. 2017

View full text Add to dashboard Cite

Spirulina platensis (SP) is a blue-green microalga that has recently raised attention not only as a nutritional component, but also as a source of bioactivities that have therapeutic effects and may find application in medicine, including cancer treatment. In the present study we determined the cytotoxic effect of S. platensis filtrates (SPF) on human colon cancer cell line Caco-2. Three concentrations of SPF were tested—1.25%, 2.5%, and 5% (v/v). We have found that the highest concentration of SPF exerts the strongest anti-proliferative and pro-apoptotic effect on Caco-2 cultures. The SPF negatively affected the morphology of Caco-2 causing colony shrinking and significant inhibition of metabolic and proliferative activity of cells. The wound-healing assay showed that the SPF impaired migratory capabilities of Caco-2. This observation was consistent with lowered mRNA levels for metalloproteinases. Furthermore, SPF decreased the transcript level of pro-survival genes (cyclin D1, surviving, and c-Myc) and reduced the autocrine secretion of Wnt-10b. The cytotoxic effect of SPF involved the modulation of the Bax and Bcl-2 ratio and a decrease of mitochondrial activity, and was related with increased levels of intracellular reactive oxygen species (ROS) and nitric oxide (NO). Moreover, the SPF also caused an increased number of cells in the apoptotic sub-G0 phase and up-regulated expression of mir-145, simultaneously decreasing expression of mir-17 and 146. Obtained results indicate that SPF can be considered as an agent with anti-cancer properties that may be used for colon cancer prevention and treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Notch signaling activation promotes tumor cell proliferation or survival and in vivo tumorigenesis through: i) direct upregulation of CCND1 (35) and MYC (44); ii) HES1-mediated CDKN1B (p27) repression and subsequent cellular proliferation (78); iii) HES1-mediated dual specificity phosphatase 1 repression and subsequent ERK activation (79); iv) HES1-mediated phosphatase and tensin homolog repression and subsequent AKT signaling activation (80); and v) HES1-mediated STAT3 activation (81,82) and cSL-independent, NF-κB-dependent interleukin 6 (IL6) upregulation, and subsequent JAK-STAT signaling activation (83). By contrast, Notch signaling activation blocks tumor cell proliferation or survival and in vivo tumorigenesis through: i) direct upregulation of CDKN1A (38,39); ii) HES1-mediated GLI family zinc finger 1 repression (84); iii) HEY1-mediated Figure 1.…”

Section: Notch Signaling In Tumor Cellsmentioning

confidence: 99%

Precision medicine for human cancers with Notch signaling dysregulation (Review)

Katoh¹,

2019

View full text Add to dashboard Cite

NOTcH1, NOTcH2, NOTcH3 and NOTcH4 are transmembrane receptors that transduce juxtacrine signals of the delta-like canonical Notch ligand (dLL)1, dLL3, dLL4, jagged canonical Notch ligand (JAG)1 and JAG2. canonical Notch signaling activates the transcription of BMI1 proto-oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context-dependent manner, while non-canonical Notch signaling activates NF-κB and Rac family small GTPase 1. Notch signaling is aberrantly activated in breast cancer, non-small-cell lung cancer and hematological malignancies, such as T-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. However, Notch signaling is inactivated in small-cell lung cancer and squamous cell carcinomas. Loss-of-function NOTCH1 mutations are early events during esophageal tumorigenesis, whereas gain-of-function NOTCH1 mutations are late events during T-cell leukemogenesis and B-cell lymphomagenesis. Notch signaling cascades crosstalk with fibroblast growth factor and WNT signaling cascades in the tumor microenvironment to maintain cancer stem cells and remodel the tumor microenvironment. The Notch signaling network exerts oncogenic and tumor-suppressive effects in a cancer stage-or (sub)type-dependent manner. Small-molecule γ-secretase inhibitors (AL101, MRK-560, nirogacestat and others) and antibody-based biologics targeting Notch ligands or receptors [ABT-165, AMG 119, rovalpituzumab tesirine (Rova-T) and others] have been developed as investigational drugs. The dLL3-targeting antibody-drug conjugate (Adc) Rova-T, and dLL3-targeting chimeric antigen receptor-modified T cells (CAR-Ts), AMG 119, are promising anti-cancer therapeutics, as are other Adcs or cARTs targeting tumor necrosis factor receptor superfamily member 17, cd19, cd22, cd30, cd79B, cd205, claudin 18.2, fibroblast growth factor receptor (FGFR)2, FGFR3, receptor-type tyrosine-protein kinase FLT3, HER2, hepatocyte growth factor receptor, NEcTIN4, inactive tyrosine-protein kinase 7, inactive tyrosine-protein kinase transmembrane receptor ROR1 and tumor-associated calcium signal transducer 2. Adcs and cARTs could alter the therapeutic framework for refractory cancers, especially diffuse-type gastric cancer, ovarian cancer and pancreatic cancer with peritoneal dissemination. Phase III clinical trials of Rova-T for patients with small-cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. Integration of human intelligence, cognitive computing and explainable artificial intelligence is necessary to construct a Notch-related knowledge-base and optimize Notch-targeted therapy for patients with cancer.

show abstract

“…Previous studies showed that HES1 is involved in oncogenesis. HES1 is highly expressed in many cancer types, including colorectal cancer cells, cervical carcinoma cells and colon cancer (19)(20)(21). A study in human lung cancers also showed that HES1 expression was at abundant level in several non-small cell lung cancer cell lines without neuroendocrine features (22), but the roles of HES5 in NSCLC remain unknown.…”

Section: Discussionmentioning

confidence: 99%

HES5 promotes cellular proliferation of non-small cell lung cancer through STAT3 signaling

Zhang

et al. 2016

Oncology Reports

View full text Add to dashboard Cite

HES5 is a transcription factor activated downstream of the Notch pathway and regulates cell differentiation in multiple tissues. Disruption of its normal expression has been associated with developmental diseases and cancer. But its role in non-small cell lung cancer (NSCLC) remains elusive. Western blot analysis and immunohistochemistry assays demonstrated that HES5 expression was frequently increased in NSCLC tumor tissues and cell lines. Moreover, immunohistochemistry analysis revealed that upregulation of HES5 expression was positively correlated with a more invasive tumor phenotype and poor prognosis. Immunoprecipitation assay indicated that HES5 directly interacted with STAT3. In addition, depletion of HES5 resulted in inhibited phosphorylation of STAT3 and decreased expression of the downstream genes. In vitro studies, using serum starvation-refeeding experiment and HES5-siRNA transfection assay demonstrated that HES5 expression promoted proliferation of NSCLC cells, while HES5 knockdown caused growth arrest of cell cycle at G0/G1 phase, decreased rate of colony formation and alleviated cellular apoptosis. Taken together, out data have delineated that HES5 might contribute to the proliferation of NSCLC by STAT3 signaling.

show abstract

Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway

Cited by 44 publications

References 48 publications

The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA

The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA

Precision medicine for human cancers with Notch signaling dysregulation (Review)

HES5 promotes cellular proliferation of non-small cell lung cancer through STAT3 signaling

Contact Info

Product

Resources

About