SphK1‐driven autophagy potentiates focal adhesion paxillin‐mediated metastasis in colorectal cancer

Wu, Jiangni; Lin, Lan; Luo, Shibo; Qiu, Xinze; Zhu, Liye; Chen, Da; Wei, Er-Dan; Fu, Zhenhua; Qin, Mengbin; Liang, Zhihai; Huang, Jiean; Liu, Shiquan

doi:10.1002/cam4.4129

Cited by 20 publications

(7 citation statements)

References 40 publications

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“…Earlier, a study showed SphK1 modulated EMT markers in CRC and its inhibition reduced cancer cell migration ( 90 ). In support of this, a study published recently demonstrated that SphK1 stimulates autophagy in CRC cells and that autophagy driven by SphK1 may promote the invasion and metastasis of CRC by promoting the expression of focal adhesion paxillin ( 45 ). In another finding, CRC cells were protected from EMT by inhibiting autophagy.…”

Section: Role Of Autophagy In Emt and Metastasismentioning

confidence: 80%

Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance

et al. 2022

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Colorectal cancer (CRC) is among the topmost malignancies for both genders. Despite the high incidence rate and advances in diagnostic tools, treatment in many cases is still ineffective. Most cancerous lesions in CRC begin as benign, followed by the development of invasive forms and metastases. The development of CRC has been linked to defects in autophagy, which plays both a pro-and anti-tumor role and is mainly context-dependent. Autophagy suppression could enhance apoptosis via p53 activation, or autophagy also promotes tumor progression by maintaining tumor growth and increasing resistance to chemotherapy. Autophagy promotes the invasion and metastasis of CRC cells via increased epithelial-mesenchymal transition (EMT). Moreover, dysbiosis of gut microbiota upregulated autophagy and metastasis markers. Autophagy responses may also modulate the tumor microenvironment (TME) via regulating the differentiation process of several innate immune cells. Treatments that promote tumor cell death by stimulating or inhibiting autophagy could be beneficial if used as an adjunct treatment, but the precise role of various autophagy-modulating drugs in CRC patients is needed to be explored. In this article, we present an overview of the autophagy process and its role in the pathogenesis and therapeutic resistance of CRC. Also, we focused on the current understanding of the role of the EMT and TME, including its relation to gut microbiota and immune cells, in autophagic manipulation of CRC. We believe that there is a potential link between autophagy, TME, EMT, and drug resistance, suggesting that further studies are needed to explore this aspect.

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Section: Role Of Autophagy In Emt and Metastasismentioning

confidence: 80%

Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance

et al. 2022

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“…Another recent study showed that UPR-induced autophagy driven by Sec62 increases the GC invasive ability [ 34 ]. Wu et al demonstrated that SphK1-induced autophagy enhances focal adhesion paxillin-mediated metastasis of CRC [ 35 ]. MST4 stimulates autophagy by phosphorylating ATG4B to promote the tumorigenicity of glioblastoma [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

MST4 promotes proliferation, invasion, and metastasis of gastric cancer by enhancing autophagy

Liu

Lin

Wang

et al. 2023

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“…Autophagy critically has been reported affecting the carcinogenesis of CRC ( Huang et al, 2018 ; Gao et al, 2022 ). For example, Sphk1-driven autophagy enhanced CRC metastasis ( Wu et al, 2021 ). However, bivalent β-Carbolines induced autophagy to depressed CRC growth ( Zhang et al, 2021 ), which means autophagy played a balance role in the occurrence and death of tumors.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of autophagy-related genes based on single-cell RNA-sequencing in colorectal cancer

et al. 2023

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Background: Colorectal cancer (CRC) is the second most common cancer in China. Autophagy plays an important role in the initiation and development of CRC. Here, we assessed the prognostic value and potential functions of autophagy-related genes (ARGs) using integrated analysis using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) and RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA).Methods: We analyzed GEO-scRNA-seq data from GEO using various single-cell technologies, including cell clustering, and identification of differentially expressed genes (DEGs) in different cell types. Additionally, we performed gene set variation analysis (GSVA). The differentially expressed ARGs among different cell types and those between CRC and normal tissues were identified using TCGA-RNA-seq data, and the hub ARGs were screened. Finally, a prognostic model based on the hub ARGs was constructed and validated, and patients with CRC in TCGA datasets were divided into high- and low-risk groups based on their risk-score, and immune cells infiltration and drug sensitivity analyses between the two groups were performed.Results: We obtained single-cell expression profiles of 16,270 cells, and clustered them into seven types of cells. GSVA revealed that the DEGs among the seven types of cells were enriched in many signaling pathways associated with cancer development. We screened 55 differentially expressed ARGs, and identified 11 hub ARGs. Our prognostic model revealed that the 11 hub ARGs including CTSB, ITGA6, and S100A8, had a good predictive ability. Moreover, the immune cell infiltrations in CRC tissues were different between the two groups, and the hub ARGs were significantly correlated with the enrichment of immune cell infiltration. The drug sensitivity analysis revealed that the patients in the two risk groups had difference in their response to anti-cancer drugs.Conclusion: We developed a novel prognostic 11-hub ARG risk model, and these hubs may act as potential therapeutic targets for CRC.

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SphK1‐driven autophagy potentiates focal adhesion paxillin‐mediated metastasis in colorectal cancer

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 20 publications

References 40 publications

Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance

Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance

MST4 promotes proliferation, invasion, and metastasis of gastric cancer by enhancing autophagy

Prognostic value of autophagy-related genes based on single-cell RNA-sequencing in colorectal cancer

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