Tumoural activation of TLR3–SLIT2 axis in endothelium drives metastasis

Tavora, Bernardo; Mederer, Tobias; Wessel, Kai J.; Ruffing, Simon; Sadjadi, Mahan; Missmahl, Marc; Ostendorf, Benjamin N.; Liu, Xuhang; Kim, Ji-Young; Olsen, Olav; Welm, Alana L.; Goodarzi, Hani; Tavazoie, Sohail F.

doi:10.1038/s41586-020-2774-y

Cited by 103 publications

(79 citation statements)

References 47 publications

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“…For example, TLR3, which belongs to the family of type I integral membrane‐associated receptors, has been reported to play an important role in immune and inflammatory responses 22 . Tavora et al 23 reported that TLR3 could induce the expression of SLIT2 and promote cancer progression. Further investigation of the expression of innate immune response‐related genes B cells will be important.…”

Section: Resultsmentioning

confidence: 99%

Landscape and dynamics of single tumor and immune cells in early and advanced‐stage lung adenocarcinoma

Chen

Huang

et al. 2021

Clinical & Translational Med

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Background Lung adenocarcinoma (LUAD) patients with different American Joint Committee on Cancer stages have different overall 5‐year survival rates. The tumor microenvironment (TME) and intra‐tumor heterogeneity (ITH) have been shown to play a crucial role in the occurrence and development of tumors. However, the TME and ITH in different lesions of LUAD have not been extensively explored. Methods We present a 204,157‐cell catalog of the TME transcriptome in 29 lung samples to systematically explore the TME and ITH in the different stages of LUAD. Traditional RNA sequencing data and complete clinical information were downloaded from publicly available databases. Results Based on these high‐quality cells, we constructed a single‐cell network underlying cellular and molecular features of normal lung, early LUAD, and advanced LUAD cells. In contrast with early malignant cells, we noticed that advanced malignant cells had a remarkably more complex TME and higher ITH level. We also found that compared with other immune cells, more differences in CD8+/CTL T cells, regulatory T cells, and follicular B cells were evident between early and advanced LUAD. Additionally, cell‐cell communication analyses, revealed great diversity between different lesions of LUAD at the single‐cell level. Flow cytometry and qRT‐PCR were used to validate our results. Conclusion Our results revealed the cellular diversity and molecular complexity of cell lineages in different stages of LUAD. We believe our research, which serves as a basic framework and valuable resource, can facilitate exploration of the pathogenesis of LUAD and identify novel therapeutic targets in the future.

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Section: Resultsmentioning

confidence: 99%

Landscape and dynamics of single tumor and immune cells in early and advanced‐stage lung adenocarcinoma

Chen

Huang

et al. 2021

Clinical & Translational Med

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“…17 Similarly, in non-haematological cancers, loss of tumoral SLIT2 enhanced metastasis, leading to cancer progression and shorter survival. 13…”

Section: Resultsmentioning

confidence: 99%

“…6: c.1769C>T:p.T590M, Fig 1C) with VAFs ranging between 15·1% and 42·7%. SLIT2 is a known tumour suppressor and key component of the SLIT/Roundabout (ROBO) pathway, which regulates various oncogenic signaling pathways 13 . Its four N‐terminal leucine‐rich repeat (LRR) domains are critical for signaling as they mediate homodimerization and interaction with ROBO molecules 14 .…”

Section: Resultsmentioning

confidence: 99%

Exome sequencing identifies SLIT2 variants in primary CNS lymphoma

et al. 2021

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SLIT2 constitutes a known tumour suppressor gene, which has not yet been implicated in the pathogenesis of primary central nervous system lymphoma (PCNSL). Performing exome sequencing on paired blood and tumour DNA samples from six treatment-na€ ıve PCNSL patients, we identified novel SLIT2 variants (p.N63S, p.T590M, p.T732S) that were associated with shorter progression-free survival in our cohort and shorter overall survival in a large validation cohort of lymphoid malignancies from the cBio Cancer Genomics Portal. WNT-and NF-jB-reporter luciferase assays suggest detected alterations are loss-of-function variants. Given the possible prognostic implications, the role of SLIT2 in PCNSL pathogenesis and progression warrants further investigation.

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“…A spontaneous breast cancer metastasis model was generated through orthotopic transplantation into mammary fat pads. This orthotopic model has helped to reveal molecular mechanisms of cancer metastasis and progression [ 22 , 23 , 24 ]. Andy J Minn et al showed that the knockdown of interleukin 13 receptor subunit alpha2 ( IL13RA2 ), secreted protein acidic and cysteine-rich ( SPARC ) and vascular cell adhesion molecule 1 ( VCAM1 ) in MDA-MB-231-LM2 cells (derived from MDA-MB-231-4175 cells) decreased lung metastatic ability after intravenous injection, but these effects did not involve orthotopic tumor growth.…”

Section: Differences In Transplantation Methods For the In Vivo Sementioning

confidence: 99%

The In Vivo Selection Method in Breast Cancer Metastasis

Nakayama¹,

Han

Kuroiwa

et al. 2021

IJMS

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Metastasis is a complex event in cancer progression and causes most deaths from cancer. Repeated transplantation of metastatic cancer cells derived from transplanted murine organs can be used to select the population of highly metastatic cancer cells; this method is called as in vivo selection. The in vivo selection method and highly metastatic cancer cell lines have contributed to reveal the molecular mechanisms of cancer metastasis. Here, we present an overview of the methodology for the in vivo selection method. Recent comparative analysis of the transplantation methods for metastasis have revealed the divergence of metastasis gene signatures. Even cancer cells that metastasize to the same organ show various metastatic cascades and gene expression patterns by changing the transplantation method for the in vivo selection. These findings suggest that the selection of metastasis models for the study of metastasis gene signatures has the potential to influence research results. The study of novel gene signatures that are identified from novel highly metastatic cell lines and patient-derived xenografts (PDXs) will be helpful for understanding the novel mechanisms of metastasis.

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Tumoural activation of TLR3–SLIT2 axis in endothelium drives metastasis

Cited by 103 publications

References 47 publications

Landscape and dynamics of single tumor and immune cells in early and advanced‐stage lung adenocarcinoma

Landscape and dynamics of single tumor and immune cells in early and advanced‐stage lung adenocarcinoma

Exome sequencing identifies SLIT2 variants in primary CNS lymphoma

The In Vivo Selection Method in Breast Cancer Metastasis

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