DOCK6 promotes chemo- and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits

Cheng, Hsiang; Tsai, Chun‐Yi; Wang, Chia Siu; Yang, Huang‐Yu; Lo, Chien Hui; Wang, Won Jing; Lee, Kam Fai; Lai, Li-Yin; Hong, Ji Hong; Chang, Yen Fang; Tsai, Ming-Ming; Yeh, Chau Ting; Wu, Chien-Hsing; Hsieh, Ching‐Chuan; Wang, Lu Hai; Chen, Wei Jan; Lin, Kwang Huei

doi:10.1038/s41388-020-01390-0

Cited by 25 publications

(19 citation statements)

References 47 publications

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“…Cancer stem cells (CSCs) are a class of tumorigenic cells that are mostly known for their self-renewal and multipotency features and make up less than 1% of the cells existing within a tumor [171,172]. Investigations on almost all types of cancer have revealed that CSCs are responsible for decreasing the tumor response to both chemo-and radiotherapy [173][174][175][176][177][178][179][180][181][182][183][184]. It seems that slowing down the cell cycle, having anti-apoptotic machinery, a high capacity for repairing DNA damage, the potency of establishing a proper environment for cancer growth, and stemness features are the main reasons why CSCs provide resistance to our common therapies [171,172,185,186].…”

Section: Cancer Stem Cellsmentioning

confidence: 99%

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

et al. 2022

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Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).

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Section: Cancer Stem Cellsmentioning

confidence: 99%

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

et al. 2022

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“…As the earliest marker of CSCs in GC, CD44 was found to be positively associated with the resistance of GC cells, and inhibition of CD44 might represent a target in the treatment of GC [7]. Importantly, accumulating experimental evidence has revealed that targeting markers of CSCs, related pathways or microenvironmental niches might impair chemoresistance [8,9]. Despite these debates about the CSC origin, stemness maintenance and continuous differentiation, an urgent and continuous need is to improve our understanding of the function and behavior of CSCs in cancer progression and chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

Targeting ZFP64/GAL-1 axis promotes therapeutic effect of nab-paclitaxel and reverses immunosuppressive microenvironment in gastric cancer

Zhu

Zhang

et al. 2022

J Exp Clin Cancer Res

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Background Chemoresistance is a main obstacle in gastric cancer (GC) treatment, but its molecular mechanism still needs to be elucidated. Here, we aim to reveal the underlying mechanisms of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resistance in GC. Methods We performed RNA sequencing (RNA-seq) on samples from patients who were resistant or sensitive to nab-paclitaxel, and identified Zinc Finger Protein 64 (ZFP64) as critical for nab-paclitaxel resistance in GC. CCK8, flow cytometry, TUNEL staining, sphere formation assays were performed to investigate the effects of ZFP64 in vitro, while subcutaneous tumor formation models were established in nude mice or humanized mice to evaluate the biological roles of ZFP64 in vivo. Chromatin immunoprecipitation sequencing (CHIP-seq) and double-luciferase reporter gene assay were conducted to reveal the underlying mechanism of ZFP64. Results ZFP64 overexpression was linked with aggressive phenotypes, nab-paclitaxel resistance and served as an independent prognostic factor in GC. As a transcription factor, ZFP64 directly binds to Galectin-1 (GAL-1) promoter and promoted GAL-1 transcription, thus inducing stem-cell like phenotypes and immunosuppressive microenvironment in GC. Importantly, compared to treatment with nab-paclitaxel alone, nab-paclitaxel plus GAL-1 blockade significantly enhanced the anti-tumor effect in mouse models, particularly in humanized mice. Conclusions Our data support a pivotal role for ZFP64 in GC progression by simultaneously promoting cellular chemotherapy resistance and tumor immunosuppression. Treatment with the combination of nab-paclitaxel and a GAL-1 inhibitor might benefit a subgroup of GC patients.

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“…CD24 can drive self-renewal and tumorigenesis of liver CSCs via STAT3-mediated Nanog pathway ( 17 ). HCC patients with high proportion of liver CSCs indicates the poor prognosis ( 19 ). Therefore, identification of the underlying mechanisms governing liver CSCs expansion may lead to the discovery of promising therapeutic strategies for HCC patients.…”

Section: Introductionmentioning

confidence: 99%

miR-186 Inhibits Liver Cancer Stem Cells Expansion via Targeting PTPN11

et al. 2021

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MicroRNAs (miRNAs) participated in the regulation of tumorigenesis, progression, metastasis, recurrence and chemo-resistance of cancers. However, the potential function of miRNAs in cancer stem cells (CSCs) or tumor-initiating cells (T-ICs) was not clearly elucidated. In the present study, we found that miR-186 expression was reduced in liver CSCs. Functional studies showed that miR-186 knockdown facilitated liver CSCs self-renewal and tumorigenesis. Conversely, forced miR-186 expression suppressed liver CSCs self-renewal and tumorigenesis. Mechanically, miR-186 downregulated PTPN11 via binding to its 3’-UTR in liver CSCs. The correlation of miR-186 and PTPN11 was confirmed in Hepatocellular carcinoma (HCC) patients’ tissues. Further study showed that interference of PTPN11 can abolished the discrepancy between miR-186 mimic and control HCC cells in self-renewal and the proportion of CSCs. Additionally, we found that miR-186 overexpression HCC cells were more sensitive to cisplatin treatment. Clinical cohort analysis showed that HCC patients with high miR-186 were benefited more from transcatheter arterial chemoembolization (TACE) treatment. In conclusion, our study demonstrates a new regulation mechanism of liver CSCs, a new target for HCC, and a biomarker for postoperative TACE.

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DOCK6 promotes chemo- and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits

Cited by 25 publications

References 47 publications

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

Targeting ZFP64/GAL-1 axis promotes therapeutic effect of nab-paclitaxel and reverses immunosuppressive microenvironment in gastric cancer

miR-186 Inhibits Liver Cancer Stem Cells Expansion via Targeting PTPN11

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