Su2001 Snail/CXCL-8 Axis Promotes Expression of the Novel Surface Marker CD58 and Self-Renewal of Tumor-Initiating Cells in Colorectal Cancer

2015 ◽  
Vol 148 (4) ◽  
pp. S-571
Author(s):  
Song Xu ◽  
Yongliang Zhu
Oncogene ◽  
2014 ◽  
Vol 34 (12) ◽  
pp. 1520-1531 ◽  
Author(s):  
S Xu ◽  
Z Wen ◽  
Q Jiang ◽  
L Zhu ◽  
S Feng ◽  
...  

2020 ◽  
Vol 26 (17) ◽  
pp. 1979-1993 ◽  
Author(s):  
Hao Wang ◽  
Guihua Cui ◽  
Bo Yu ◽  
Meiyan Sun ◽  
Hong Yang

Cancer stem cells (CSCs), also known as tumor-initiating cells, are a sub-population of tumor cells found in many human cancers that are endowed with self-renewal and pluripotency. CSCs may be more resistant to conventional anticancer therapies than average cancer cells, as they can easily escape the cytotoxic effects of standard chemotherapy, thereby resulting in tumor relapse. Despite significant progress in related research, effective elimination of CSCs remains an unmet clinical need. CSCs are localized in a specialized microenvironment termed the niche, which plays a pivotal role in cancer multidrug resistance. The niche components of CSCs, such as the extracellular matrix, also physically shelter CSCs from therapeutic agents. Colorectal cancer is the most common malignancy worldwide and presents a relatively transparent process of cancer initiation and development, making it an ideal model for CSC niche research. Here, we review recent advances in the field of CSCs using colorectal cancer as an example to illustrate the potential therapeutic value of targeting the CSC niche. These findings not only provide a novel theoretical basis for in-depth discussions on tumor occurrence, development, and prognosis evaluation, but also offer new strategies for the targeted treatment of cancer.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiahui Xu ◽  
Xiaoli Yang ◽  
Qiaodan Deng ◽  
Cong Yang ◽  
Dong Wang ◽  
...  

AbstractEnhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ERα trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2045
Author(s):  
Agnieszka Gornowicz ◽  
Anna Szymanowska ◽  
Mariusz Mojzych ◽  
Robert Czarnomysy ◽  
Krzysztof Bielawski ◽  
...  

Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have anti-tumor activity in vitro and in vivo. The aim of the study was to synthesize a novel 1,2,4-triazine sulfonamide derivative and check its anticancer potential in DLD-1 and HT-29 colon cancer cells. The biological studies included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. The concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. We demonstrated that the novel compound was able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM-1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines. The novel compound represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim.


2013 ◽  
Vol 74 (1) ◽  
pp. 341-352 ◽  
Author(s):  
Cleo Yi-Fang Lee ◽  
Yuan Lin ◽  
Scott V. Bratman ◽  
Weiguo Feng ◽  
Angera H. Kuo ◽  
...  

2021 ◽  
Vol 27 ◽  
Author(s):  
Huai Wang ◽  
Jiankang Yang

The epidemic of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in the world pose a global health emergency. Cancer has been identified as a risk factor for the novel Coronavirus disease 2019 (COVID-19). The ACE2 and TMPRSS2 have been implicated in SARS-CoV-2 infection for mediating viral entry into the host cell. However, a systematic analysis of aberrant expression of ACE2 and TMPRSS2 was not yet reported in multiple human cancers. Here, we analyzed gene expression of ACE2 and TMPRSS2 across 31 types of tumors. Notably, overexpression of ACE2 and TMPRSS2 have been observed in colorectal cancer including colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). In addition, the colorectal tumors with upregulated gene expressing presented with decreased DNA methylation levels. DNA methylation might be one of the reasons for abnormal expression of ACE2 and TMPRSS2. Conclusively, colorectal cancer was the only cancer with the upregulated expression of ACE2 and TMPRSS2. More care of colorectal cancer patients is needed in multiple cancers affected by the COVID-19 outbreak.


2018 ◽  
Vol 115 (22) ◽  
pp. E5086-E5095 ◽  
Author(s):  
Liang Xu ◽  
Ye Chen ◽  
Anand Mayakonda ◽  
Lynnette Koh ◽  
Yuk Kien Chong ◽  
...  

Competitive BET bromodomain inhibitors (BBIs) targeting BET proteins (BRD2, BRD3, BRD4, and BRDT) show promising preclinical activities against brain cancers. However, the BET protein-dependent glioblastoma (GBM)-promoting transcriptional network remains elusive. Here, with mechanistic exploration of a next-generation chemical degrader of BET proteins (dBET6), we reveal a profound and consistent impact of BET proteins on E2F1- dependent transcriptional program in both differentiated GBM cells and brain tumor-initiating cells. dBET6 treatment drastically reduces BET protein genomic occupancy, RNA-Pol2 activity, and permissive chromatin marks. Subsequently, dBET6 represses the proliferation, self-renewal, and tumorigenic ability of GBM cells. Moreover, dBET6-induced degradation of BET proteins exerts superior antiproliferation effects compared to conventional BBIs and overcomes both intrinsic and acquired resistance to BBIs in GBM cells. Our study reveals crucial functions of BET proteins and provides the rationale and therapeutic merits of targeted degradation of BET proteins in GBM.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Ali Aamar ◽  
Zeeshan Butt ◽  
Kamraan Madhani ◽  
Iqra Hussain ◽  
Joel Garsten ◽  
...  

Background. In the United States, patients wear a one-piece, reusable cloth gown during colonoscopy procedures. Many patients report embarrassment related to bodily exposure during colonoscopy. This may limit participation in colorectal cancer screening programs. Aims. To assess whether the use of a novel, disposable patient garment (Privacy Pants, Jackson, MS), which increases patient coverage, can reduce embarrassment related to bodily exposure and increase colonoscopy acceptance rates. Methods. Patients were offered a novel gown, and they completed questionnaires before and after colonoscopy. Results. A total of 120 patients participated. 54% were female and 82% were Caucasian. The novel gown had high overall satisfaction (8.3) and was associated with a sense of respect during the procedure (9.4). 67% (80) of the patients had a prior colonoscopy, and of these, 76% would request a novel gown over a traditional gown for future procedures. Among all study participants, a high rate of acceptability for repeat colonoscopy if recommended by their doctors was reported (mean of 9.4). Nonwhites were more likely to have a concern for embarrassment addressed by using novel gowns as compared to whites (P value 0.02). Conclusion. All participants, particularly women and nonwhite participants, reported high rates of respect and satisfaction and decrease in embarrassment utilizing the novel gown during colonoscopy. Patients who had prior colonoscopy with a traditional gown preferred the novel garment. A novel procedure gown may enhance colonoscopy acceptance by minimizing embarrassment.


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