scholarly journals Radiation-Induced Overexpression of TGFβ and PODXL Contributes to Colorectal Cancer Cell Radioresistance through Enhanced Motility

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2087
Author(s):  
Hyunjung Lee ◽  
Joon-Seog Kong ◽  
Seung-Sook Lee ◽  
Areumnuri Kim
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Surface Glycoprotein ◽  
Tissue Samples ◽  
Cell Surface Glycoprotein ◽  
Matrix Deposition ◽  
Metastatic Relapse ◽  
Radiation Induced ◽  
And Migration

The primary cause of colorectal cancer (CRC) recurrence is increased distant metastasis after radiotherapy, so there is a need for targeted therapeutic approaches to reduce the metastatic-relapse risk. Dysregulation of the cell-surface glycoprotein podocalyxin-like protein (PODXL) plays an important role in promoting cancer-cell motility and is associated with poor prognoses for many malignancy types. We found that CRC cells exposed to radiation demonstrated increased TGFβ and PODXL expressions, resulting in increased migration and invasiveness due to increased extracellular matrix deposition. In addition, both TGFβ and PODXL were highly expressed in tissue samples from radiotherapy-treated CRC patients compared to those from patients without this treatment. However, it is unclear whether TGFβ and PODXL interactions are involved in cancer-progression resistance after radiation exposure in CRC. Here, using CRC cells, we showed that silencing PODXL blocked radiation-induced cell migration and invasiveness. Cell treatment with galunisertib (a TGFβ-pathway inhibitor) also led to reduced viability and migration, suggesting that its clinical use may enhance the cytotoxic effects of radiation and lead to the effective inhibition of CRC progression. Overall, the results demonstrate that downregulation of TGFβ and its-mediated PODXL may provide potential therapeutic targets for patients with radiotherapy-resistant CRC.

scholarly journals Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiao Wu ◽  
Sai-Ching Jim Yeung ◽  
Sicheng Liu ◽  
Aiham Qdaisat ◽  
Dewei Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Cancer Patient ◽  
Nutrition Support ◽  
Immunodeficient Mice ◽  
The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

scholarly journals miR-142-3p Modulates Cell Invasion and Migration via PKM2-Mediated Aerobic Glycolysis in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
JunYu Ren ◽  
Wenliang Li ◽  
Guoqing Pan ◽  
Fengchang Huang ◽  
Jun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pyruvate Kinase ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Aerobic Glycolysis ◽  
Cancer Cell Invasion ◽  
Human Colorectal Cancer ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues

Decreased expression of miR-142-3p was observed in human cancers. However, the function and mechanism of miR-142-3p in human colorectal cancer remain obscure. The expressions of miR-142-3p in human colorectal cancer tissues and cell lines were measured by RT-qPCR. The effects of miR-142-3p on cell invasion and migration were detected by transwell assays. The efficiency of aerobic glycolysis was determined by glucose consumption and lactate production. Dual-luciferase reporter assays were performed to confirm the correlation between miR-142-3p and pyruvate kinase isozyme M2 (PKM2). The level of PKM2 was assessed by western blotting. Our results showed that the expression of miR-142-3p was decreased both in human colorectal cancer tissues and in cells. Overexpression of miR-142-3p in cell line attenuated colorectal cancer cell invasion and migration. About the underlying mechanism, we found that miR-142-3p modulated aerobic glycolysis via targeting pyruvate kinase M2 (PKM2). In addition, we demonstrated PKM2 and PKM2-mediated aerobic glycolysis contributes to miR-142-3p-mediated colorectal cancer cell invasion and migration. Hence, these data suggested that miR-142-3p was a potential therapeutic target for the treatment of human colorectal cancer.

Down-Regulated LncRNA-HOTAIR Suppressed Colorectal Cancer Cell Proliferation, Invasion, and Migration by Mediating p21

2018 ◽  
Vol 63 (9) ◽  
pp. 2320-2331 ◽  
Author(s):  
Kai Lin ◽  
Hong Jiang ◽  
Ling-Ling Zhang ◽  
Yi Jiang ◽  
Yu-Xian Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Invasion And Migration ◽  
And Migration ◽  
Lncrna Hotair

Long Non-Coding RNA-Colon Cancer Associated Transcript 1 Down-Regulation Inhibits Cell Proliferation and Promotes Apoptosis in Colorectal Cancer Through Enhancing miR-152 Expression

2020 ◽  
Vol 10 (12) ◽  
pp. 1766-1772
Author(s):  
Jindong Li ◽  
Xi Wang ◽  
Xin Huang ◽  
Na Li ◽  
Ya Ling ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Viability ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Biological Effects ◽  
Colorectal Cancer Cell ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Cancer Tissue ◽  
Colorectal Cancer Progression

Colorectal cancer is a common malignant cancer that is characterized by high mortality rate. CCAT1 is a type of newly discovered lncRNA. This research was conducted to study the role of CCAT1 in colorectal cancer. The findings showed that there was significant up-regulation of CCAT1 expression in colorectal cancer. Then, online bioinformatic database and dual-luciferase reporter assay to prove CCAT1 and miR-152 have direct binding sites. Many researches demonstrated that miR-152 played a crucial role in development of colorectal cancer. Therefore, we then explored the relationship between CCAT1 and miR-152 in colorectal cancer. qRT-PCR analysis showed that miR-152 was lowly expressed in cancer tissue and cells. We then explored the effect of CCAT1 and miR-152 on the biological effects of colorectal cancer cells. MiR-152 up-regulation significantly reduced colorectal cancer cell viability and enhanced apoptosis. Furthermore, CCAT1-shRNA inhibited colorectal cancer cell viability and enhanced cell apoptosis were significantly eliminated by miR-152 inhibitor. Combined with all results, CCAT1/miR-152 axis was related to colorectal cancer progression regulation, which might be used as new therapeutic targets for colorectal cancer treatment.

scholarly journals Long non-coding RNA AGER-1 inhibits colorectal cancer progression through sponging miR-182

2020 ◽  
Vol 35 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Mingzhu Lin ◽  
Yinyan Li ◽  
Jianfeng Xian ◽  
Jinbin Chen ◽  
Yingyi Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Tumor Development ◽  
Vital Role ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Colorectal Cancer Progression ◽  
And Migration ◽  
Long Non Coding Rna

Objective: Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termed lnc-AGER-1, has been discovered in cancers, and this lncRNA was reported to exert an anti-tumor effect. However, its biological mechanism remains unelucidated in colorectal cancer. Methods: A total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression of lnc-AGER-1 by the quantitative Real-time PCR (qRT-PCR), and a series of functional assays was executed to uncover the role of this lncRNA on colorectal cancer. Results: We found that the expression of lnc-AGER-1 in the tumor tissues was significantly down-regulated, while compared with adjacent normal tissues (0.0115 ± 0.0718 vs. 0.0347 ± 0.157; P < 0.0001). Also, lnc-AGER-1 was observably associated with clinical T status (r = −0.184, P = 0.024). Patients with advanced T status exerted a significantly lower level of lnc-AGER-1 than those with early T status (20.0% vs. 40.7%, P = 0.021). Over-expression of lnc-AGER-1 inhibited cell proliferation and migration efficiency, and induced cell cycle arrest at the G0/G1 phase, and promoted cell apoptosis. Further research proved that lnc-AGER-1 altered the expression of its neighbor gene, AGER, through acting as a competing endogenous RNA for miR-182 in colorectal cancer. Conclusion: lnc-AGER-1 has a suppressive role in colorectal cancer development via modulating AGER, which may serve as a target for colorectal cancer diagnosis and treatment.

scholarly journals Probing the mechanisms of extracellular vesicle biogenesis and function in cancer

2018 ◽  
Vol 46 (5) ◽  
pp. 1137-1146 ◽  
Author(s):  
Arash Latifkar ◽  
Richard A. Cerione ◽  
Marc A. Antonyak
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Extracellular Vesicle ◽  
Rna Transcripts ◽  
Main Class ◽  
Vesicle Biogenesis ◽  
And Migration ◽  
And Function ◽  
Cell Phenotypes

Tumor cells interact with each other, and their surroundings, using a variety of mechanisms to promote virtually all aspects of cancer progression. One such form of intercellular communication that has been attracting considerable attention from the cancer community and the pharmaceutical industry in recent years involves the ability of cancer cells to generate multiple distinct types of non-classical secretory vesicles, generally referred to as extracellular vesicles (EVs). Microvesicles (MVs) represent one of the major classes of EVs and are formed as a result of the outward budding and fission of the plasma membrane. The other main class of EVs is exosomes, which are generated when multivesicular bodies fuse with the cell surface and release their contents into the extracellular space. Both MVs and exosomes have been shown to contain bioactive cargo, including proteins, metabolites, RNA transcripts, microRNAs, and DNA that can be transferred to other cancer cells and stimulate their growth, survival, and migration. However, cancer cell-derived EVs also play important roles in helping re-shape the tumor microenvironment to support tumor expansion and invasive activity, dampen immune responses, as well as enter the circulation to help promote metastatic spread. Here, we provide an overview of what is currently known regarding how the different classes of EVs are generated and contribute to various cancer cell phenotypes. Moreover, we highlight how some of the unique properties of EVs are being used for the development of novel diagnostic and clinical applications.

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