scholarly journals EGFL6 Promotes Colorectal Cancer Cell Growth and Mobility and the Anti-cancer Property of Anti-EGFL6 Antibody

2020 ◽  
Author(s):  
Ting-Yi Sung ◽  
Han-Li Huang ◽  
Chun-Chun Cheng ◽  
Fu-Ling Chang ◽  
Po-Li Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Animal Experiments ◽  
Patient Characteristics ◽  
Cancer Biomarker ◽  
Blue Staining ◽  
Migration And Invasion ◽  
Metal Stents ◽  
Αvβ3 Integrin ◽  
Phage Display Technology

Abstract BackgroundA reliable cancer biomarker will be critical for advanced colorectal cancer (CRC) therapeutic approaches since current treatments are limited to certain patient characteristics, such as age, sex, comorbidities and patients received self-expandable metal stents implantations. The association of epidermal growth factor-like domain 6 (EGFL6) with cancer development has been reported. Here, we focused on the role of EGFL6 in CRC progression and its clinical relevance. MethodsAn anti-EGFL6 antibody was generated by phage display technology to investigate the potential therapeutic efficacy in CRC. Methylene blue staining was applied to investigate the EGFL6 expression in CRC patients and animal tissue. Protein and DNA level of EGFL6 expression as well as related pathway investigation were determined by western blot and quantitative real time PCR. Silence EGFL6 by siRNA transfection, transwell migration and invasion assay were performed to verify EGFL6 function. Student t test, Kruskal-Wallis test and multiple comparisons were used to statistical analysis results. ResultsSignificant EGFL6 expression was found in colon tissues from patients and spontaneous tumorigenesis mouse but not in normal tissue. Furthermore, we found EGFL6 could enhance cancer cell migration, invasion and proliferation in CRC via up-regulating ERK/ AKT pathway, as well as reducing ADAMTS1 and Snail expression. We also found EGFL6 regulates cell abilities through EGFR/αvβ3 integrin receptors. By conducting animal experiments, our anti-EGFL6 antibody, EGFL6-E5-IgG, showed tumor inhibition and anti-metastasis ability. Furthermore, no impact on angiogenesis and wound healing by using EGFL6-E5-IgG were observed. ConclusionsWe demonstrated that EGFL6 plays a role in CRC tumorigenesis and tumor progression, indicating that EGFL6 is a potential cancer biomarker and therapeutic target worth further investigation.

scholarly journals EGFL6 promotes colorectal cancer cell growth and mobility and the anti-cancer property of anti-EGFL6 antibody

2020 ◽  
Author(s):  
Ting-Yi Sung ◽  
Han-Li Huang ◽  
Chun-Chun Cheng ◽  
Fu-Ling Chang ◽  
Po-Li Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Animal Experiments ◽  
Transcript Level ◽  
Patient Characteristics ◽  
Cancer Biomarker ◽  
Metal Stents ◽  
Αvβ3 Integrin ◽  
Cancer Cell Growth ◽  
Phage Display Technology

Abstract BackgroundA reliable cancer biomarker will be critical for advanced colorectal cancer (CRC) therapeutic approaches since current treatments are limited to certain patient characteristics, such as age, sex, comorbidities and patients received self-expandable metal stents implantations. The association of epidermal growth factor-like domain 6 (EGFL6) with cancer development has been reported. Here, we focused on the role of EGFL6 in CRC progression and its clinical relevance. An anti-EGFL6 antibody was generated by phage display technology to investigate the potential therapeutic efficacy in CRC. Student t test, Kruskal-Wallis test and multiple comparisons were used to statistical analysis results.ResultsSignificant EGFL6 expression was found in colon tissues from patients and spontaneous tumorigenesis mouse but not in normal tissue. Under hypoxia condition, EGFL6 expression were enhanced in protein and transcript-level. Furthermore, we found EGFL6 could enhance cancer cell migration, invasion and proliferation in CRC via up-regulating ERK/ AKT pathway, as well as reducing ADAMTS1 and Snail expression. We also found EGFL6 regulates cell abilities through EGFR/αvβ3 integrin receptors. By conducting animal experiments, our anti-EGFL6 antibody, EGFL6-E5-IgG, showed tumor inhibition and anti-metastasis ability. Furthermore, no impact on angiogenesis and wound healing by using EGFL6-E5-IgG were observed.ConclusionsWe demonstrated that EGFL6 plays a role in CRC tumorigenesis and tumor progression, indicating that EGFL6 is a potential cancer biomarker and therapeutic target worth further investigation.

scholarly journals EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting-Yi Sung ◽  
Han-Li Huang ◽  
Chun-Chun Cheng ◽  
Fu-Ling Chang ◽  
Po-Li Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Hypoxic Condition ◽  
Αvβ3 Integrin ◽  
Integrin Receptors ◽  
Cancer Cell Growth ◽  
Phage Display Technology ◽  
Display Technology ◽  
Epidermal Growth

Abstract Background The availability of a reliable tumor target for advanced colorectal cancer (CRC) therapeutic approaches is critical since current treatments are limited. Epidermal growth factor-like domain 6 (EGFL6) has been reported to be associated with cancer development. Here, we focused on the role of EGFL6 in CRC progression and its clinical relevance. In addition, an anti-EGFL6 antibody was generated by phage display technology to investigate its potential therapeutic efficacy in CRC. Results EGFL6 expression significantly increased in the colon tissues from CRC patients and mice showing spontaneous tumorigenesis, but not in normal tissue. Under hypoxic condition, EGFL6 expression was enhanced at both protein and transcript levels. Moreover, EGFL6 could promote cancer cell migration invasion, and proliferation of CRC cells via up-regulation of the ERK/ AKT pathway. EGFL6 also regulated cell migration, invasion, proliferation, and self-renewal through EGFR/αvβ3 integrin receptors. Treatment with the anti-EGFL6 antibody EGFL6-E5-IgG showed tumor-inhibition and anti-metastasis abilities in the xenograft and syngeneic mouse models, respectively. Moreover, EGFL6-E5-IgG treatment had no adverse effect on angiogenesis and wound healing Conclusions We demonstrated that EGFL6 plays a role in CRC tumorigenesis and tumor progression, indicating that EGFL6 is a potential therapeutic target worth further investigation.

scholarly journals Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Simona Mareike Lüttgenau ◽  
Christin Emming ◽  
Thomas Wagner ◽  
Julia Harms ◽  
Justine Guske ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Scaffolding Protein ◽  
Migration And Invasion ◽  
Tight Junction Formation ◽  
Cell Metastasis ◽  
Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

scholarly journals TGF‐β‐induced IGFBP‐3 is a key paracrine factor from activated pericytes that promotes colorectal cancer cell migration and invasion

2020 ◽  
Vol 14 (10) ◽  
pp. 2609-2628 ◽  
Author(s):  
Rocío Navarro ◽  
Antonio Tapia‐Galisteo ◽  
Laura Martín‐García ◽  
Carlos Tarín ◽  
Cesáreo Corbacho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Colorectal Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Paracrine Factor ◽  
Cell Migration And Invasion ◽  
Igfbp 3

scholarly journals Overexpression of lncRNA NLIPMT Inhibits Colorectal Cancer Cell Migration and Invasion by Downregulating TGF-β1

2020 ◽  
Vol Volume 12 ◽  
pp. 6045-6052
Author(s):  
Yongkang An ◽  
Shuangxi Zhang ◽  
Jing Zhang ◽  
Qing Yin ◽  
Haitao Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Colorectal Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Circ_0007031 enhances tumor progression and promotes 5-fluorouracil resistance in colorectal cancer through regulating miR-133b/ABCC5 axis

2020 ◽  
Vol 29 (4) ◽  
pp. 531-542
Author(s):  
Xiaowen He ◽  
Jun Ma ◽  
Mingming Zhang ◽  
Jianhua Cui ◽  
Hao Yang
Keyword(s):  
Colorectal Cancer ◽  
Colony Formation ◽  
Human Cancer ◽  
Animal Experiments ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cell Progression ◽  
Rna Immunoprecipitation

Colorectal cancer (CRC) remains one of the most commonly diagnosed malignancies worldwide. Circular RNAs (circRNAs) are being found to play crucial roles in human cancer, including CRC. The purpose of this study was to explore the function and mechanism of circ_0007031 on CRC progression and 5-fluorouracil (5-FU) resistance. The levels of circ_0007031, ATP-binding cassette subfamily C member 5 (ABCC5) and miR-133b were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell survival and proliferation were detected by the 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Cell colony formation was evaluated using a standard colony formation assay. Transwell assays were performed to determine cell migration and invasion. Targeted correlations among circ_0007031, miR-133b and ABCC5 were verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown assays. Animal experiments were performed to observe the role of circ_0007031 in vivo. Our data indicated that circ_0007031 up-regulation was associated with CRC resistance to 5-FU. Circ_0007031 knockdown repressed CRC cell proliferation, migration and invasion and enhanced 5-FU sensitivity. Circ_0007031 directly interacted with miR-133b. Moreover, circ_0007031 knockdown regulated CRC cell progression and 5-FU sensitivity by miR-133b. ABCC5 was a direct target of miR-133b, and circ_0007031 mediated ABCC5 expression via acting as a miR-133b sponge. Furthermore, miR-133b overexpression regulated CRC cell progression and sensitivity to 5-FU by down-regulating ABCC5. Additionally, circ_0007031 knockdown suppressed tumor growth in vivo. Our current work had led to the identification of circ_0007031 knockdown that repressed CRC cell malignant progression and enhanced 5-FU sensitivity via regulating ABCC5 expression by sponging miR-133b.

scholarly journals Inhibition to Epithelial-Mesenchymal Transition and Metastatic Potential In Colorectal Cancer Cell By Combination of Traditional Chinese Medicine Formulation Jiedu Sangen Decoction and PD-L1 Inhibitor

2020 ◽  
Vol 19 ◽  
pp. 153473542097248
Author(s):  
Feiyu Shan ◽  
Leitao Sun ◽  
Leyin Zhang ◽  
Kaibo Guo ◽  
Qingying Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Laser Scanning Microscopy ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Mesenchymal Transition

Background: Jiedu Sangen Decoction (JSD), a traditional Chinese medicine formula, has been widely applied in the treatment of gastrointestinal cancer, especially in colorectal cancer. Our study mainly aimed to assess the combined efficacy of Jiedu Sangen aqueous extract (JSAE) and a PD-L1 inhibitor (PI) in colon cancer cells migration and invasion, along with epithelial-mesenchymal transition, and then provide deep insights into the potential mechanism. Methods: We explored the inhibitory effects on invasion and metastasis and the reverse effect on EMT process in CT-26 colon cancer cell via Transwell migration assay, Matrigel invasion assay and confocal laser scanning microscopy. Furthermore, regulation in expression of EMT-related proteins and molecular biomarkers and underlying signal pathway proteins were detected through Western blotting and IHC. Results: The combination of JSD and PD-L1 inhibitor could inhibit migration, invasive ability and EMT of CT-26 cells in a concentration-dependent manner. Meanwhile, JSD combined with PD-L1 inhibitor could also remarkably reverse EMT and metastasis in vivo. In addition, the protein expression of N-cadherin, Slug, Snail, Vimentin was down-regulated along with E-cadherin s up-regulation with the combination of JSD and PD-L1 inhibitor, while that of PI3K/AKT was notably down-regulated. Conclusions: These findings indicated that JSAE and a PD-L1 inhibitor could drastically inhibit the migration and invasion of colorectal cancer by reversing EMT through the PI3K/AKT signaling pathway.

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