Journal Browser

► Journal Browser

Special Issue Information

Dear Colleagues,

The role of the microenvironment in cancer is widely recognized by the scientific community. In addition to malignant and non-malignant cells and immune and inflammatory cells, the cancer microenvironment includes secreted proteins, small molecules, the extracellular matrix, and blood vessels. This complex microenvironment constantly interacts with and influences (positively or negatively) the development and growth of the tumour.

This Special Issue aims to highlight recent advances in tumour microenvironment research and to present current findings and opinions on the microenvironment in cancer. We welcome original research or state-of-the-art reviews on all aspects of the tumour microenvironment in cancer. Research areas may include (but are not limited to) pathogenesis, new therapeutic strategies, therapeutic resistance, early diagnosis and biomarkers, and basic and translational research related to the microenvironment in cancer.

Dr. Marcello Manfredi
Prof. Dr. Marco Falasca
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

tumour microenvironment
immune evasion
omics and microenvironment characterization
inflammatory cells
secretome characterization
cancer
tumour development
tumour inhibition
biomolecules released in the tumour microenvironment
immune infiltrate
tumour–stroma crosstalk
nerves in the tumour microenvironment

Published Papers (2 papers)

Download All Papers

Research

17 pages, 4892 KiB

Open AccessArticle

Ephexin3/ARHGEF5 Together with Cell Migration Signaling Partners within the Tumor Microenvironment Define Prognostic Transcriptional Signatures in Multiple Cancer Types

by Dante Gustavo Juan-Guadarrama, Yarely Mabell Beltrán-Navarro, Guadalupe Reyes-Cruz and José Vázquez-Prado

Int. J. Mol. Sci. 2023, 24(22), 16427; https://doi.org/10.3390/ijms242216427 - 17 Nov 2023

Viewed by 1107

Abstract

Cancer cell migration involves a repertoire of signaling proteins that lead cytoskeleton reorganization as a critical step in metastatic dissemination. RhoGEFs are multidomain effectors that integrate signaling inputs to activate the molecular switches that orchestrate actin cytoskeleton reorganization. Ephexins, a group of five RhoGEFs, play oncogenic roles in invasive and metastatic cancer, leading to a mechanistic hypothesis about their function as signaling nodes assembling functional complexes that guide cancer cell migration. To identify clinically significant Ephexin signaling partners, we applied three systematic data mining strategies, based on the screening of essential Ephexins in multiple cancer cell lines and the identification of coexpressed signaling partners in the TCGA cancer patient datasets. Based on the domain architecture of encoded proteins and gene ontology criteria, we selected Ephexin signaling partners with a role in cytoskeletal reorganization and cell migration. We focused on Ephexin3/ARHGEF5, identified as an essential gene in multiple cancer cell types. Based on significant coexpression data and coessentiality, the signaling repertoire that accompanies Ephexin3 corresponded to three groups: pan-cancer, cancer-specific and coessential. To further select the Ephexin3 signaling partners likely to be relevant in clinical settings, we first identified those whose high expression was statistical linked to shorter patient survival. The resulting Ephexin3 transcriptional signatures represent significant accumulated risk, predictive of shorter survival, in 17 cancer types, including PAAD, LUAD, LGG, OSC, AML, KIRC, THYM, BLCA, LIHC and UCEC. The signaling landscape that accompanies Ephexin3 in various cancer types included the tyrosine kinase receptor MET and the tyrosine phosphatase receptor PTPRF, the serine/threonine kinases MARK2 and PAK6, the Rho GTPases RHOD, RHOF and RAC1, and the cytoskeletal regulator DIAHP1. Our findings set the basis to further explore the role of Ephexin3/ARHGEF5 as an essential effector and signaling hub in cancer cell migration. Full article

(This article belongs to the Special Issue Tumor Microenvironment 2023)

► Show Figures

Figure 1

21 pages, 5852 KiB

Open AccessArticle

Targeting Tumor Microenvironment Akt Signaling Represents a Potential Therapeutic Strategy for Aggressive Thyroid Cancer

by Saied Mirshahidi, Isabella J. Yuan, Alfred Simental, Steve C. Lee, Nathaniel R. Peterson, Pedro A. Andrade Filho, Thomas Murry, Penelope Duerksen-Hughes and Xiangpeng Yuan

Int. J. Mol. Sci. 2023, 24(6), 5471; https://doi.org/10.3390/ijms24065471 - 13 Mar 2023

Viewed by 1315

Abstract

Effects of the tumor microenvironment (TME) stromal cells on progression in thyroid cancer are largely unexplored. Elucidating the effects and underlying mechanisms may facilitate the development of targeting therapy for aggressive cases of this disease. In this study, we investigated the impact of TME stromal cells on cancer stem-like cells (CSCs) in patient-relevant contexts where applying in vitro assays and xenograft models uncovered contributions of TME stromal cells to thyroid cancer progression. We found that TME stromal cells can enhance CSC self-renewal and invasiveness mainly via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. The disruption of Akt signaling could diminish the impact of TME stromal cells on CSC aggressiveness in vitro and reduce CSC tumorigenesis and metastasis in xenografts. Notably, disrupting Akt signaling did not cause detectable alterations in tumor histology and gene expression of major stromal components while it produced therapeutic benefits. In addition, using a clinical cohort, we discovered that papillary thyroid carcinomas with lymph node metastasis are more likely to have elevated Akt signaling compared with the ones without metastasis, suggesting the relevance of Akt-targeting. Overall, our results identify PI3K/Akt pathway-engaged contributions of TME stromal cells to thyroid tumor disease progression, illuminating TME Akt signaling as a therapeutic target in aggressive thyroid cancer. Full article

(This article belongs to the Special Issue Tumor Microenvironment 2023)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Tumor Microenvironment 2023

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (2 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI