Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data

Silva, Victor Menezes; Gomes, Jéssica Alves; Tenório, Luciana Lucena; Neta, Genilda Castro de Omena; Paixão, Karen da Costa; Duarte, Ana Kelly Fernandes; Silva, Gabriel Cerqueira Braz da; Ferreira, Ricardo Jansen Santos; Koike, Bruna Del Vechio; Marques, Carolinne de Sales; Miguel, Rafael Danyllo da Silva; Queiroz, Aline Cavalcanti de; Pereira, Luciana Xavier; Fraga, Carlos Alberto de Carvalho

doi:10.18632/oncotarget.27204

Cited by 16 publications

(21 citation statements)

References 28 publications

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“…Activated SCs have been shown to be present in a variety of cancers (18,(38)(39)(40)(41). We demonstrate that cancer cells activate SCs in a manner related to that seen after nerve injury and activate the transcription factor c-Jun.…”

Section: Discussionmentioning

confidence: 65%

Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion

Deborde

Gusain

Powers

et al. 2022

Preprint

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Nerves are a component of the tumor microenvironment contributing to cancer progression, but the role of cells from nerves in facilitating cancer invasion remains poorly understood. Here we show that Schwann cells (SCs) activated by cancer cells collectively function as Tumor Activated Schwann cell Tracks (TASTs) that promote cancer cell migration and invasion. Non-myelinating SCs form TASTs and have cell gene expression signatures that correlate with diminished survival in patients with pancreatic ductal adenocarcinoma. In TASTs, dynamic SCs form tracks that serve as cancer pathways and apply forces on cancer cells to enhance cancer motility. These SCs are activated by c-Jun, analogous to their reprogramming during nerve repair. This study reveals a mechanism of cancer cell invasion that co-opts a wound repair process and exploits the ability of SCs to collectively organize into tracks. These findings establish a novel paradigm of how cancer cells spread and reveal therapeutic opportunities.

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Section: Discussionmentioning

confidence: 65%

Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion

Deborde

Gusain

Powers

et al. 2022

Preprint

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“…In multiple types of cancer, such as thyroid cancer, salivary duct carcinoma, cutaneous squamous cell carcinoma, pancreatic cancer, and colon cancer, when the nerve is damaged or invaded by cancer cells, the number of GFAP-positive SCs increases [ 33 , 36 ]. Silva et al used bioinformatic analysis to investigate the transcriptomics of SCs among lung cancer samples and found that dedifferentiation-related pathways were overexpressed [ 56 ]. In cutaneous melanoma, the local neurodegenerative response caused by cancer is very similar to the nerve repair process induced by skin injury.…”

Section: Scs In the “Tumor-nerve Niche”mentioning

confidence: 99%

Schwann Cells in the Tumor Microenvironment: Need More Attention

Sun

Chen

2022

Journal of Oncology

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The tumor microenvironment (TME), which is composed of various cell components and signaling molecules, plays an important role in the occurrence and progression of tumors and has become the central issue of current cancer research. In recent years, as a part of the TME, the peripheral nervous system (PNS) has attracted increasing attention. Moreover, emerging evidence shows that Schwann cells (SCs), which are the most important glial cells in the PNS, are not simply spectators in the TME. In this review article, we focused on the up-to-date research progress on SCs in the TME and introduced our point of view. In detail, we described that under two main tumor-nerve interaction patterns, perineural invasion (PNI) and tumor innervation, SCs were reprogrammed and acted as important participants. We also investigated the newest mechanisms between the interactions of SCs and tumor cells. In addition, SCs can have profound impacts on other cellular components in the TME, such as immune cells and cancer-associated fibroblasts (CAFs), involving immune regulation, tumor-related pain, and nerve remodeling. Overall, these innovative statements can expand the scope of the TME, help fully understand the significant role of SCs in the tumor-nerve-immune axis, and propose enlightenments to innovate antitumor therapeutic methods and future research.

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“…Among all of the residual effects, we observe that most of them are from methylation. For example, SLC2A1, ECT2, TNS4, DKK1, and GNPNAT1 are found to be associated with the survival of lung cancer patients [ 25 , 26 , 27 , 28 , 29 ].…”

Section: Analysis Of Tcga Datamentioning

confidence: 99%

Integrating Multi–Omics Data for Gene-Environment Interactions

Fan

et al. 2021

BioTech

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Gene-environment (G×E) interaction is critical for understanding the genetic basis of complex disease beyond genetic and environment main effects. In addition to existing tools for interaction studies, penalized variable selection emerges as a promising alternative for dissecting G×E interactions. Despite the success, variable selection is limited in terms of accounting for multidimensional measurements. Published variable selection methods cannot accommodate structured sparsity in the framework of integrating multiomics data for disease outcomes. In this paper, we have developed a novel variable selection method in order to integrate multi-omics measurements in G×E interaction studies. Extensive studies have already revealed that analyzing omics data across multi-platforms is not only sensible biologically, but also resulting in improved identification and prediction performance. Our integrative model can efficiently pinpoint important regulators of gene expressions through sparse dimensionality reduction, and link the disease outcomes to multiple effects in the integrative G×E studies through accommodating a sparse bi-level structure. The simulation studies show the integrative model leads to better identification of G×E interactions and regulators than alternative methods. In two G×E lung cancer studies with high dimensional multi-omics data, the integrative model leads to an improved prediction and findings with important biological implications.

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Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data

Cited by 16 publications

References 28 publications

Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion

Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion

Schwann Cells in the Tumor Microenvironment: Need More Attention

Integrating Multi–Omics Data for Gene-Environment Interactions

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