CD133 overexpression

In agreement with these results, murine and human CRC biopsies colonized with CoPEC exhibited higher expression levels of OCT-3/4 and NANOG than biopsies devoid of CoPEC. CoPEC might aggravate CRCs by inducing the emergence of cancer stem cells that are highly resistant to chemotherapy.

Our study demonstrates that the upregulation of CD133 is linked to cellular proliferation and protects PTC from apoptosis in DKD and high glucose induced PTC injury. We propose that heightened CD133 expression may facilitate cellular self-protective responses during the initial stages of high glucose exposure. However, its sustained increase is associated with the pathological progression of DKD. In conclusion, CD133 exhibits dual roles in the advancement of DKD, necessitating further investigation.

This study revealed PARD3 as a potential preventive target of liver tumorigenesis via TIC regulation.

Contrary to prior assumptions, the G12V NRAS mutant form is sufficient to elicit hepatocarcinogenesis in the mouse. Furthermore, the upregulation of the MAPK cascade was paralleled by the overexpression of DUSP4, DUSP6, and CD133 in vivo and in vitro. Therefore, DUSP4 and DUSP6 might fine-tune the excessive MAPK activation, a mechanism that can potentially be harnessed therapeutically.

These data provide an approach for achieving both intracellular inhibitory molecule, SHP-1 deletion and CD133 CAR gene over-expression in human T cells. And SHP-1 could be a new potential target for adoptive CAR T cells immunotherapy.

Down-regulation of Wnt antagonist secreted frizzled-related protein 4 (sFRP4) in GBM and GSCs, indicating activation of the Wnt/β-catenin pathway, which could be involved in the conversion of iPSCs to CSCs. From future perspectives, our study will help in the creation of a rapid cell-based platform for understanding the complexity of GBM.

Our findings revealed that SERPINA12 is preferentially overexpressed in epithelial HCC CD133+ cells and is a key contributor to HCC initiation and progression by driving an AKT/β-catenin feed-forward loop.

APEX1 knockdown increased the sensitivity of CD133 GBC-SD cells to 5-Fluorouracil via facilitating cell necrosis and apoptosis...Mechanistically, APEX1 affected these malignant properties via upregulating Jagged1 in CD133 GBC-SD cells. Thus, APEX1 is a promising prognostic biomarker, and a potential therapeutic target for GBC.

The present study shows that metastatic CD133 + pancreatic TICs have higher PLD1 expression and its enzymatic product PA which regulate the metastatic ability of these TICs. Targeting PLD1 could lead to a potential therapeutic breakthrough especially in reducing tumor metastasis in PDAC patients.

In vitro lncRNA HOXA11-AS silencing inhibited OSCC stem cell stemness by targeting the miR-518a-3p/PDK1 axis, thus enhancing OSCC cell radiosensitivity.

CD133 may therefore activate a survival pathway where (1) increased AKT phosphorylation and activation induces (2) BAD phosphorylation and inactivation, (3) decreases BAX activation, and (4) reduces caspases-3 and -9 activity and caspase-mediated PARP cleavage, leading to apoptosis suppression and drug resistance in melanoma. Targeting nodes of the AKT and MAPK survival pathways with both trametinib and AZD5363 highlights the potential for combination therapies for NRAS-mutant melanoma stem cells for the development of more effective treatments for patients with high-risk melanoma.

Collectively, our findings revealed that SERPINA12 is preferentially overexpressed in epithelial HCC CD133+cells and is a key contributor to HCC initiation and progression by driving an AKT/β-catenin feed-forward loop.

CD133 is overexpressed in colon CSCs and morin treatment has reduced the CD133 expression in HCT116 and CT26 colon cancer cell lines. Our research outcome has explored the anti-cancer stem cell potency of morin via targeting the PUM1 protein and further reducing the colon spheroids formation and reducing the CD133 expression in colon cancer cells.

HIF-1α, ANXA3 and CD133 were overexpressed in human colon cancer and showed positive correlations among themselves. The expression of HIF-1α, ANXA3 and CD133 were closely related to the size of the tumor, lymphatic metastasis and clinical stage of colon cancer, which indicated that they could be promising biomarkers for the study of colon CSCs and treatment of colon carcinoma.

AKIP1 regulates the malignant behaviors and stemness of GBM via regulating multiple carcinogenetic pathways.

In this study, Cs5, a novel specific aptamer with a dissociation constant in the nanomolar range, was developed using the cell-SELEX strategy from engineered CD133-expressing cells, and doxorubicin (Dox) was loaded into the Cs5 aptamer to form a chimera...The in vitro and in vivo results demonstrated the highly efficient therapy and low toxicity of the chimera. Given the overexpression of CD133 in various tumors, our work provides a promising tool for specific cell identification and a wide range of applications in the field of targeted cancer therapy.

ALDH1 overexpression was significantly associated with disease relapse in invasive cervical carcinoma treated by chemoradiation (P<0.01). Determination of ALDH1 levels in pre-treatment cervical biopsies of invasive cervical carcinoma may be useful for prediction of response to chemoradiation, with high levels predicting for a poor response.

Then, in rescue experiments, HIF-1α overexpression and β-catenin overexpression both promoted cell invasion, CD133 cell proportion, and sphere number/1,000 cells, which also attenuated the effect of AKIP1 knockdown on these functions in AGS cells and MKN45 cells. AKIP1 promotes cell invasion and stemness via activating HIF-1α and β-catenin signaling pathways in gastric cancer under hypoxia condition.

Finally, we demonstrated that in vivo CCL-486 treatment decreased CD133+ percentage and inhibited tumor growth in PDX models. In conclusion, we provided insights on the efficacy of a novel miRNA-based compound to hit CD133+ lung CSCs, setting the basis for new combined therapeutic strategies.

Cytotoxicity studies in MDA-MB-231-LM2 cells revealed maximum kill in drug loaded anti-CD133 NPs, which was significantly higher than for either non-targeted, drug-loaded nanoparticles or blank nanoparticles (p<0.05). Overall, these studies indicate the potential for using anti-CD133 scFv-Fc in conjunction with FNP-produced silicate prodrug nanoparticles of paclitaxel for efficient targeting of CSCs.

Drug delivery of aCD133 aptamer coupled with doxorubicin has been found to inhibit the growth of liver cancer cells. XTT cell viability and apoptotic assays such as AnnexinV-PI flow cytometry analysis revealed that the triple combination with trametinib, mebendazole and the CD133 aptamer was the most effective in inducing apoptotic cell death, even in the doxycycline-induced CD133-overexpressing melanoma cells. Further studies will use preclinical in vivo mouse xenograft models to investigate the effects on tumor growth of CD133 RNA aptamers in combination treatments, potentially making it available for clinical trials aiming to improve patient response to therapeutics against drug-resistant melanoma cells.

Combination marker analysis showed that co-expression of NQO1 and CD133 was associated with poor outcome. This study suggests that analyzing the expression status of CD133 alone and co-expression of NQO1 and CD133 may have additional value in predicting the outcome of TAE/TACE-treated HCC patients.

ALDH1 overexpression was significantly associated with disease relapse in invasive cervical carcinoma treated by chemoradiation (P<0.01). Determination of ALDH1 levels in pre-treatment cervical biopsies of invasive cervical carcinoma may be useful for prediction of response to chemoradiation, with high levels predicting for a poor response.

Moreover, activating AKT or overexpressing CTNNB1 attenuated the effect of SENP2 overexpression on stemness and sorafenib sensitivity in Huh7 and Hep3B cells. SENP2 suppresses HCC stemness and increases sorafenib sensitivity through inactivating the AKT/GSK3β/CTNNB1 signaling pathway.

Moreover, miR-34a overexpression reduced the enchaining effects of prominin 1 on LC cell proliferation. Therefore, miR-34a might suppress LC cell proliferation by targeting prominin 1.

Increased CD133 protein expression is associated with sooner distant tumor recurrence on MRI in glioblastoma patients and patients with high-grade gliomas and improved TTL on MRI in glioblastoma patients. Based on the current evidence from 1086 patients with high-grade gliomas, CD133 overexpression is a valuable marker to predict tumor relapse and tumor recurrence patterns in patients with high-grade gliomas.

Overall, these results suggest that HDAC9 inhibition plays a functional role in the modulation of EMT properties in CSC-like prostate cancer cells. Therefore, these findings could facilitate the development of therapeutic strategies for controlling prostate cancer metastasis.

Interestingly, the diminution of Akt expression by specific siAkt effectively reversed suppressive activity of TDB targeting on the CSC phenotype in human lung cancer cells. These findings provide promising evidence of the inhibitory effect of TDB against lung CSCs via suppression of Akt/GSK3β/β-catenin cascade and related proteins, which would facilitate the development of this bibenzyl natural compound as a novel CSC-targeted therapeutic approach for lung cancer treatment.

High CEACAM5 expression in colorectal cancer cells is firmly associated with the CD133-positive colorectal CSC phenotype, but it is unlikely that CD133 directly regulates CEACAM5 expression.

Moreover, the combination treatment of jorunnamycin A (0.5 μM) and cisplatin (25 μM) also diminished CD133-overexpresssing cells presented in CSC-enriched spheroids. Thus, evidence on the regulatory functions of jorunnamycin A may facilitate the development of this marine-derived compound as a novel chemotherapy agent that targets CSCs in lung cancer treatment.

Furthermore, serum deprivation increased the amount of endogenous CD133 protein, which was regulated at least in part by PI3K. Thus, it is highly likely that CD133 contributes to the acquisition/maintenance of the resistance to stress arising from nutrient deficiency in early avascular tumor tissues.

A novel mRNA 3’UTR shortening machinery was shown to mediate the simultaneous overexpression of ABCG2 and CD133 in SP and CSC cells. It may represent useful drug target for circumvention of resistance and eradication of CSCs.

When Elk-1 expression is silenced, the expression of these stemness genes is decreased. We propose that Elk-1 is a transcription factor upstream of these genes, regulating the self-renewal of CD133+ BTICs.

More importantly, we found by RT-PCR aberrant activation and upregulation of Wnt/ β-catenin and its downstream targeting genes, such as DKK1 and AXIN2 in SP cells. These findings suggest that development of new anticancer drugs which target Wnt/β-catenin signaling might effectively exterminate the SP cells and aid in disease free survival.

Knockdown of miR-150-5p contributed to CD133- cells with stem cell-like phenotype, whereas overexpression of miR-150-5p suppressed CD133+ glioma stem cell-like characteristics. In conclusion, miR-150-5p inhibited the progression of glioma through controlling stem cell-like characteristics by regulating the Wnt/β-catenin pathway, providing a novel target for glioma treatment.

Finally, PARK7 knockdown increased mouse survival and IR sensitivity in vivo. Based on these data, we propose that PARK7 plays a pivotal role in the maintenance of stemness and therapeutic resistance in GSCs.

The nanoparticles could be used as a T2-weighted magnetic resonance imaging contrast media, and also applied during hyperthermia and chemotherapy to display a synergistic anticancer effect. Therefore, the superparamagnetic iron oxide@poly(sodium styrene sulfonate)/irinotecan/human serum albumin-anti-CD133 nanoparticles are a powerful candidate for future antitumor strategies.

Thus, although CSCs 5-FU chemoresistance appears to be independently to MMR status, hMLH1 might play a key role in CSC response to 5-FU. New drugs exploding these differences could benefit the prognostic of patients with CRC.