scholarly journals Tunicamycinvia ER stress mediated 6th hour time point aggravates cell migration, cell invasion and cell proliferation in colonic epithelial cells

2021 ◽  
pp. 100007
Author(s):  
Rohit Gundamaraju ◽  
Ravichandra Vemuri ◽  
Ranga Rao Ambati ◽  
Lakshminarayana Rangaswamy ◽  
Wenying Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Er Stress ◽  
Cell Invasion ◽  
Colonic Epithelial Cells ◽  
Time Point

scholarly journals Tunicamycin aggravates cell migration, cell invasion and cell proliferation in colonic epithelial cells

2021 ◽  
Author(s):  
Rohit Gundamaraju ◽  
Ravichandra vemuri ◽  
Ranga Rao Ambati ◽  
Lakshminarayana Rangaswamy ◽  
Wenying Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Cell Invasion ◽  
Gastrointestinal Cancers ◽  
Colonic Epithelial Cells ◽  
Positive Correlation ◽  
Preliminary Results ◽  
Clinical Conditions

Abstract Aim: Endoplasmic reticular stress (ERS) has been well-documented in escalating metastasis in clinical conditions. There has been a debate on its role in cancer portraying it as a double-edged sword. However, there is no evidence of increased cell migration and cell invasion under increased ERS by tunicamycin(TUN) 10μg/mL. Methods: In this study, we treated colonic epithelial cells (LS174T cells) with TUN and measured cell proliferation (by Ki67+ assay), cell migration and cell invasion at the 6th hour specifically. Results: Our results have demonstrated a positive correlation between TUN and cell migration, cell invasion, and proliferation. TUN treatment has significantly escalated cell invasion, migration and proliferation in LS174T cells. Conclusion: These preliminary results clearly suggest that TUN might promote metastasis of gastrointestinal cancers.

scholarly journals Bitter melon protects against ER stress in LS174T colonic epithelial cells

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Dale A. Kunde ◽  
Wai Chin Chong ◽  
Prathiba V. Nerurkar ◽  
Kiran D.K. Ahuja ◽  
Jeremy Just ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Er Stress ◽  
Bitter Melon ◽  
Colonic Epithelial Cells

scholarly journals Hydroxyphenyl Butanone Induces Cell Cycle Arrest through Inhibition of GSK3β in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Songyan Zhang ◽  
Yunfeng Wang ◽  
Haopeng Zhang ◽  
Chengming Sun ◽  
Shuwei Dang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Epithelial Cells ◽  
Tumor Cells ◽  
Colony Formation ◽  
Colorectal Cancer Cell Line ◽  
Colonic Epithelial Cells ◽  
Low Concentration ◽  
Key Factor

Background. Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/β-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention. Methods. Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3β knockdown. Results. Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3β in Wnt/β-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells. Conclusion. This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3β and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.

scholarly journals PDGFRB knockdown rescues the efficacy of chemotherapy in metastatic gastric cancer patients

2021 ◽  
Author(s):  
Yang Tian ◽  
Wei Song ◽  
Shuping Yang ◽  
Zheng Chen ◽  
Ming Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Prognostic Factors ◽  
Cell Invasion ◽  
Cox Regression ◽  
Survival Curve ◽  
Metastatic Gastric Cancer ◽  
Akt Pathway

IntroductionThis study aimed to investigate the effect of PDGFRB on the efficacy of neoadjuvant chemotherapy (NAC) in metastatic gastric cancer (MGC).Material and methodsThe data from Gene Expression Omnibus (GEO) were analyzed to screen differentially expressed genes (DEGs). PDGFRB expression in cells were assessed by qRT-PCR and immunohistochemistry. Transwell, MTT and colony form assays were applied to determine the abilities of cell migration, cell invasion and cell proliferation. The association of core gene and PI3K/AKT pathway were identified through STRING database and western blot detection. Differences in overall survival (OS) among different patients were analyzed through Kaplan-Meier survival curve and prognostic factors were analyzed by Cox regression.ResultsHigh expression of PDGFRB and were found in gastric cancer through GEO data and MGC patients with combination chemotherapy resistance of docetaxel, cisplatin and S-1 (DCS therapy). Furthermore, the down-regulation of PDGFRB by PDGFRB shRNA or sunitinib malate could decrease cell migration, cell invasion and cell proliferation in resistant cells. Those findings were verified by in vivo experiments. Meanwhile, PDGFRB overexpression was accompany with the activation of PI3K/AKT pathway. In addition, the OS of patients in highly expressed PDGERB group were lower than that in lowly PDGFRB expressed group and PDGFRB, TNM staging and differentiation degree were the prognostic factors for MGC patients.ConclusionsPDGFRB knockdown could rescue the efficacy of chemotherapy in MGC and PDGFRB could serve as a novel marker for the prognosis of MGC.

TGF beta 1 promotes actin cytoskeleton reorganization and migratory phenotype in epithelial tracheal cells in primary culture

1996 ◽  
Vol 109 (9) ◽  
pp. 2207-2219 ◽  
Author(s):  
S. Boland ◽  
E. Boisvieux-Ulrich ◽  
O. Houcine ◽  
A. Baeza-Squiban ◽  
M. Pouchelet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Actin Cytoskeleton ◽  
Primary Culture ◽  
Tgf Beta ◽  
Cytoskeleton Reorganization ◽  
Extracellular Matrix Components ◽  
Migratory Phenotype

In the present study we have investigated the effects of transforming growth factor beta (TGF beta 1) on rabbit tracheal epithelial cells in primary culture, with respect to cell proliferation and differentiation. Epithelial tracheal cells derived from an explant plated on an extracellular matrix, formed an outgrowth resulting from cell division and cell migration. TGF beta 1 treatment produced a negative effect on cell proliferation, but in contrast, promoted a marked enhancement of cell migration and increase in outgrowth surface. TGF beta 1 induced marked cell shape changes, including cell spreading and lack of stratification, associated with reduced cell-cell contacts and increased cell-substratum anchorage, as seen by electron microscopic observations. Immunocytological studies demonstrated major TGF beta 1-induced actin cytoskeleton reorganization, corresponding to the development of a basal stress fiber network and decrease of the annular cell border, without affecting the tight junctions. The migratory phenotype was approached by microcinematography which clearly showed that TGF beta 1 triggered a stimulatory effect on migration of epithelial cells, determined using an image analyzing system. Present findings suggest a beneficial role for TGF beta 1 during wound healing in providing the acquisition of a migratory phenotype, with a higher capacity to migrate either on collagen or on different extracellular matrix components including laminin and fibronectin. Conversely, present data are not consistent with a squamous response to TGF beta 1, since metaplastic differentiation did not occur, as characterized by cytokeratin expression and cross-linked envelopes formation.

Interleukin-8 stimulates the migration of human colonic epithelial cells in vitro

1999 ◽  
Vol 97 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Andrew J. WILSON ◽  
Keith BYRON ◽  
Peter R. GIBSON
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
In Vitro Model ◽  
Interleukin 8 ◽  
Colonic Epithelium ◽  
Dependent Manner ◽  
Colonic Epithelial Cells ◽  
Tnf Α ◽  
Vitro Model

The migration of colonic epithelial cells (restitution) is an important event in the repair of mucosal injuries. Interleukin-8 (IL-8) is a physiological initiator of the chemotactic migration of leucocytes. This study aimed to determine whether IL-8 had a similar effect on migration in an in vitro model of wounded colonic epithelium. Cell migration over 24 h was assessed in circular wounds made in confluent monolayers of the human colon cancer cell line LIM1215. This migration was stimulated in a concentration-dependent manner by IL-8, with maximal effects of approx. 1.75-fold above basal migration. The motogenic effect of IL-8 was mediated independently of effects on cell proliferation. In contrast, it was partially dependent upon gene transcription and protein synthesis and involved the activation of pertussis-toxin-sensitive G-proteins. The short-chain fatty acids, acetate, propionate, butyrate and valerate, the activator of protein kinase C (phorbol-12-myristate-13-acetate) and tumour necrosis factor-α (TNF-α) all stimulated the secretion of IL-8. However, only the motogenic effect of TNF-α was dependent upon IL-8. In conclusion, IL-8 stimulated cell migration in an in vitro model of colonic epithelium, whereas the motogenic effect of at least one physiologically relevant factor was dependent upon an increase in its endogenous levels. If IL-8 stimulates colonic epithelial restitution in vivo, this would have ramifications for the control of repair processes following wounding of the colonic mucosa.

Hepatocyte growth factor promotes colonic epithelial regeneration via Akt signaling

2007 ◽  
Vol 293 (1) ◽  
pp. G230-G239 ◽  
Author(s):  
Masami Kanayama ◽  
Terumi Takahara ◽  
Yutaka Yata ◽  
Feng Xue ◽  
Eiji Shinno ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Akt Signaling ◽  
Colonic Epithelial Cells ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) can promote the regeneration of injured organs, including HGF gene therapy by electroporation (EP) for liver injury. In this study, we investigated the effect of HGF on dextran sulfate sodium-induced colitis and tried to clarify the regenerative mechanisms of colonic epithelial cells and the signaling pathway involved. Colitis was induced by dextran sulfate sodium in mice, together with HGF gene transfer by EP. On day 10, the colitis was evaluated histologically and by Western blot analysis. The colonic epithelial cell line MCE301 was exposed to HGF protein, and its proliferation and activated signaling pathway were analyzed. In vivo, the histological score improved and the number of Ki-67-positive epithelial cells increased in the HGF-treated mice compared with the controls. Western blot analysis showed enhanced expression of phospho-Akt in the HGF-treated mice compared with the controls. In vitro, HGF stimulated the proliferation of MCE301 cells. There was enhanced phospho-Akt expression for more than 48 h after HGF stimulation, although phospho-ERK1/2 was enhanced for only 10 min. LY-294002 or Akt small interfering RNA suppressed cell proliferation induced by HGF. Thus HGF induces the proliferation of colonic epithelial cells via the phosphatidylinositol 3-kinase/Akt signaling pathway. HGF gene therapy can attenuate acute colitis via epithelial cell proliferation through the PI3K/Akt pathway. These data suggested that HGF gene therapy by EP may be effective for the regeneration and repair of injured epithelial cells in inflammatory bowel disease.

Epidermal growth factor inhibits Ca(2+)-dependent Cl- transport in T84 human colonic epithelial cells

1996 ◽  
Vol 271 (3) ◽  
pp. C914-C922 ◽  
Author(s):  
J. M. Uribe ◽  
C. M. Gelbmann ◽  
A. E. Traynor-Kaplan ◽  
K. E. Barrett
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Inhibitory Effect ◽  
Inhibitory Pathway ◽  
T84 Cells ◽  
Colonic Epithelial Cells ◽  
Cl Secretion ◽  
Epidermal Growth ◽  
Time Point

This study examined whether epidermal growth factor (EGF) inhibits Ca(2+)-dependent Cl- secretion by T84 cells. Basolateral EGF inhibited Cl- secretion induced by carbachol or thapsigargin, without blocking the rise in intracellular Ca2+. Studies have shown that carbachol renders T84 cells refractory to subsequent stimulation by thapsigargin, an effect ascribed to D-myo-inositol 3,4,5,6-tetrakisphosphate [D-Ins(3,4,5,6)P4]. EGF also increased DL-Ins(3,4,5,6)P4 to a maximum of 170% above control. However, despite the fact that EGF inhibited Cl- secretion at 1 min, DL-Ins(3,4,5,6)P4 was not elevated at this time point. EGF plus carbachol had a greater inhibitory effect on Cl- secretion than either alone, indicating the likely involvement of an additional inhibitory pathway activated by EGF. Staurosporine did not alter the ability of EGF to inhibit Cl- secretion or increase DL-Ins(3,4,5,6)P4. In contrast, genistein inhibited the rise in DL-Ins(3,4,5,6)P4 and partially reversed EGF's inhibitory effect on Cl- secretion. In conclusion, EGF and carbachol can both inhibit Cl- secretion via D-Ins(3,4,5,6)P4, whereas EGF also generates an additional inhibitory signal.

scholarly journals Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 578-590 ◽  
Author(s):  
Nick Powell ◽  
Eirini Pantazi ◽  
Polychronis Pavlidis ◽  
Anastasia Tsakmaki ◽  
Katherine Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Epithelial Cells ◽  
Er Stress ◽  
Functional Role ◽  
Chronic Colitis ◽  
Colonic Epithelial Cells ◽  
Interleukin 22 ◽  
Er Stress Response

ObjectiveThe functional role of interleukin-22 (IL22) in chronic inflammation is controversial, and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic colitis and probed mechanisms of IL22-mediated regulation of colonic epithelial cells.DesignTo investigate the functional role of IL22 in chronic colitis and how it regulates colonic epithelial cells, we employed a three-dimentional mini-gut epithelial organoid system, in vivo disease models and transcriptomic datasets in human IBD.ResultsAs well as inducing transcriptional modules implicated in antimicrobial responses, IL22 also coordinated an endoplasmic reticulum (ER) stress response transcriptional programme in colonic epithelial cells. In the colon of patients with active colonic Crohn’s disease (CD), there was enrichment of IL22-responsive transcriptional modules and ER stress response modules. Strikingly, in an IL22-dependent model of chronic colitis, targeting IL22 alleviated colonic epithelial ER stress and attenuated colitis. Pharmacological modulation of the ER stress response similarly impacted the severity of colitis. In patients with colonic CD, antibody blockade of IL12p40, which simultaneously blocks IL12 and IL23, the key upstream regulator of IL22 production, alleviated the colonic epithelial ER stress response.ConclusionsOur data challenge perceptions of IL22 as a predominantly beneficial cytokine in IBD and provide novel insights into the molecular mechanisms of IL22-mediated pathogenicity in chronic colitis. Targeting IL22-regulated pathways and alleviating colonic epithelial ER stress may represent promising therapeutic strategies in patients with colitis.Trial registration numberNCT02749630.

Sign in / Sign up

Export Citation Format

Share Document