Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer

Unterleuthner, Daniela; Neuhold, Patrick; Schwarz, Katharina; Janker, Lukas; Neuditschko, Benjamin; Nivarthi, Harini; Crnčec, Ilija; Kramer, Nina; Unger, Christine; Hengstschläger, Markus; Eferl, Robert; Moriggl, Richard; Sommergruber, Wolfgang; Gerner, Christopher; Dolznig, Helmut

doi:10.1007/s10456-019-09688-8

Cited by 219 publications

(165 citation statements)

References 71 publications

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“…Next, WNT2, a secreted glycoprotein, was predicted to be a potential target gene of miR-30a-3p by bioinformatics analysis. It has been reported that WNT2 can promote the development of tumors [42][43][44], and the WNT2/β-Catenin signaling pathway is related to the malignant biological functions of GC [45][46][47]. This protein drew our attention.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-Catenin pathway

Cao

Zhang

et al. 2020

Preprint

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Background : Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism). Methods: Through RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2’-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization. Results: CircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo . CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7. Conclusions: CircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-Catenin pathway

Cao

Zhang

et al. 2020

Preprint

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“…Multiple classes of molecules, including growth factors, cytokines, proteases, and extracellular matrix proteins, carried by CAF-EV mediate stroma-tumour-cell interaction [61]. Several studies sustain the role of EV derived from CAF primary cell lines on tumour proliferation, survival, migration, and invasion [62,63]. A significant role of CAF-EV in promoting the migration and invasion of oral squamous cell carcinoma (OSCC) cells has been reported [64].…”

Section: Caf-evmentioning

confidence: 99%

Extracellular Vesicles in the Tumour Microenvironment: Eclectic Supervisors

Cavallari

Camussi

Brizzi

2020

IJMS

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The tumour microenvironment (TME) plays a crucial role in the regulation of cell survival and growth by providing inhibitory or stimulatory signals. Extracellular vesicles (EV) represent one of the most relevant cell-to-cell communication mechanism among cells within the TME. Moreover, EV contribute to the crosstalk among cancerous, immune, endothelial, and stromal cells to establish TME diversity. EV contain proteins, mRNAs and miRNAs, which can be locally delivered in the TME and/or transferred to remote sites to dictate tumour behaviour. EV in the TME impact on cancer cell proliferation, invasion, metastasis, immune-escape, pre-metastatic niche formation and the stimulation of angiogenesis. Moreover, EV can boost or inhibit tumours depending on the TME conditions and their cell of origin. Therefore, to move towards the identification of new targets and the development of a novel generation of EV-based targeting approaches to gain insight into EV mechanism of action in the TME would be of particular relevance. The aim here is to provide an overview of the current knowledge of EV released from different TME cellular components and their role in driving TME diversity. Moreover, recent proposed engineering approaches to targeting cells in the TME via EV are discussed.

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“…Galectin-1 originating from CAFs in gastric cancer promotes proliferation, migration, and tube formation of vascular endothelial cells and enhanced tumor angiogenesis in vivo [ 43 ]. The upregulation of WNT2 in colorectal CAFs stimulates the migration and invasion of endothelial cells and promotes angiogenesis through the production of pro-angiogenic factors [ 44 ]. VEGF-bound small extracellular vesicles are secreted by CAFs to enhance tumor angiogenesis [ 45 ].…”

Section: Cancer-associated Fibroblasts (Cafs)mentioning

confidence: 99%

Long Non-Coding RNAs as Regulators of Interactions between Cancer-Associated Fibroblasts and Cancer Cells in the Tumor Microenvironment

Ahn

Kim²

2020

IJMS

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Long non-coding RNAs (lncRNAs) regulate diverse physiological and pathological processes via post-transcriptional, post-translational, and epigenetic mechanisms. They are also involved in tumor initiation, progression, and metastasis by functioning as key players in the tumor microenvironment. Cancer-associated fibroblasts (CAFs) promote tumor initiation, progression, metastasis, drug resistance, and immunosuppression, which can be modulated by lncRNAs. LncRNAs regulate the intrinsic properties of CAFs or cancer cells intracellularly or function extracellularly through exosomal secretion. In-depth studies on the mechanisms of lncRNA functions will enable their clinical use as diagnosis/prognosis markers and therapeutic targets in cancer treatment.

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Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer

Cited by 219 publications

References 71 publications

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-Catenin pathway

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-Catenin pathway

Extracellular Vesicles in the Tumour Microenvironment: Eclectic Supervisors

Long Non-Coding RNAs as Regulators of Interactions between Cancer-Associated Fibroblasts and Cancer Cells in the Tumor Microenvironment

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