A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity

Veß, Astrid; Blache, Ulrich; Leitner, Laura; Kurz, Angela R.M.; Ehrenpfordt, Anja; Sixt, Michael; Posern, Guido

doi:10.1242/jcs.200899

Cited by 16 publications

(20 citation statements)

References 46 publications

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“…In granulocyte-macrophage colony-stimulating factor (GM-CSF) generated bone marrow-derived MΦ, phosphorylation of PXN by Pyk2/FAK initiates proteolysis of PXN, and subsequent cell rounding and detachment in a CD45-dependent manner 62 . Similarly, TNS3 acts as a linker between the extracellular matrix and the cytoskeleton, and has been described as a negative regulator of cell migration in cancer cells 45,46 . Apparently, TNS3 is regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype

et al. 2019

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Tumor-immune cell interactions shape the immune cell phenotype, with microRNAs (miRs) being crucial components of this crosstalk. How they are transferred and how they affect their target landscape, especially in tumor-associated macrophages (TAMs), is largely unknown. Here we report that breast cancer cells have a high constitutive expression of miR-375, which is released as a non-exosome entity during apoptosis. Deep sequencing of the miRome pointed to enhanced accumulation of miR-375 in TAMs, facilitated by the uptake of tumor-derived miR-375 via CD36. In macrophages, miR-375 directly targets TNS3 and PXN to enhance macrophage migration and infiltration into tumor spheroids and in tumors of a xenograft mouse model. In tumor cells, miR-375 regulates CCL2 expression to increase recruitment of macrophages. Our study provides evidence for miR transfer from tumor cells to TAMs and identifies miR-375 as a crucial regulator of phagocyte infiltration and the subsequent development of a tumor-promoting microenvironment.

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Section: Discussionmentioning

confidence: 99%

Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype

et al. 2019

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“…In the suspension subpopulation of MDA-MB-468 breast cancer cells, loss of cell-matrix adhesion results in a dramatic downregulation of TNS3, whereas TNS1, TNS2 and other main cell matrix adaptor proteins, such as vinculin and the talins, are not affected (Veß et al, 2017). Re-expressing TNS3 in the suspended MDA-MB-468 cells rescues their adhesion, whereas knockdown of TNS3 in the adherent parental MDA-MB-468 cells reduces their attachment (Veß et al, 2017), demonstrating that TNS3 is a positive regulator of cell adhesion.…”

Section: Cell Adhesionmentioning

confidence: 99%

Tensins – emerging insights into their domain functions, biological roles and disease relevance

Liao

2021

Journal of Cell Science

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Tensins are a family of focal adhesion proteins consisting of four members in mammals (TNS1, TNS2, TNS3 and TNS4). Their multiple domains and activities contribute to the molecular linkage between the extracellular matrix and cytoskeletal networks, as well as mediating signal transduction pathways, leading to a variety of physiological processes, including cell proliferation, attachment, migration and mechanical sensing in a cell. Tensins are required for maintaining normal tissue structures and functions, especially in the kidney and heart, as well as in muscle regeneration, in animals. This Review discusses our current understanding of the domain functions and biological roles of tensins in cells and mice, as well as highlighting their relevance to human diseases.

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“…Paxillin is a focal adhesion adapter protein that, depending on its subcellular localization, can positively or negatively regulate cell migration [147][148][149]. Similarly, tensin 3 acts as a link between the extracellular matrix and the cytoskeleton and functionally contributes to the switch between adhesive and non-adhesive states in cancer cells, including breast cancer [150,151]. In tissue microarrays of mammary carcinoma patients, miR-375 was elevated in breast cancer tissue as compared to normal breast tissue, and positively correlated with the number of infiltrated macrophages.…”

Section: Guo Et Al Investigated Mechanisms Of Breast Cancer Invasionmentioning

confidence: 99%

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

Syed

Frank

Raue

et al. 2019

Cells

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MicroRNAs (miRs) significantly contribute to the regulation of gene expression, by virtue of their ability to interact with a broad, yet specific set of target genes. MiRs are produced and released by almost every cell type and play an important role in horizontal gene regulation in the tumor microenvironment (TME). In the TME, both tumor and stroma cells cross-communicate via diverse factors including miRs, which are taking central stage as a therapeutic target of anti-tumor therapy. One of the immune escape strategies adopted by tumor cells is to release miRs as a Trojan horse to hijack circulating or tumor-localized monocytes/macrophages to tune them for pro-tumoral functions. On the other hand, macrophage-derived miRs exert anti-tumor functions. The transfer of miRs from host to recipient cells depends on the supramolecular structure and composition of miR carriers, which determine the distinct uptake mechanism by recipient cells. In this review, we provide a recent update on the miR-mediated crosstalk between tumor cells and macrophages and their mode of uptake in the TME.(TNF-α), and provoke the secretion of pro-inflammatory cytokines including interleukin-1 (IL-1), IL-6, IL-12, IL-23, and TNF-α and reactive nitrogen and oxygen intermediates (RNI, ROI) [5]. In contrast, anti-inflammatory stimuli such as IL-4, IL-13, IL-10, and glucocorticoid or immune complexes (IC) plus LPS induce macrophages to an M2 phenotype. This type is characterized by a decreased production of pro-inflammatory cytokines, increased production of anti-inflammatory cytokines (e.g., IL-10), and factors that mediate immunosuppression and tissue remodeling. M2 macrophages have been divided into further subgroups. The M2a type is generated in response to IL-3 and IL-13, while M2b macrophages respond to immune complexes and Toll-like receptor (TLR) activation. M2c macrophages represent deactivated macrophages that suppress pro-inflammatory cytokines, while the M2d type represents a regulatory macrophage [6] that is often grouped with TAMs [5,7,8]. In line with these varied responses, Janus-faced macrophage functions are largely determined by their microenvironment rather than their genetic imprint [9,10]. In tumors and during the resolution of inflammation, hijacked macrophages attain pro-tumor or wound healing phenotypes due to tumor-derived factors [11], which emerge as a target for tumor therapy [12,13]. TAMs expressing classical activation markers produce pro-inflammatory cytokines and reactive oxygen species (ROS) and, thus, are crucial for tumor cell killing [14,15]. The high degree of plasticity demonstrated by macrophages in pathological conditions can be attributed to a) dynamic regulation of gene expression and b) rapid activation of signaling cascades that determine their effector functions. Signaling cascades triggered by local environmental cues and controlling the transcriptional machinery, ultimately determine the effector functions of macrophages in the tumor microenvironment (TME). Hence, understanding and modulating these ...

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A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity

Cited by 16 publications

References 46 publications

Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype

Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype

Tensins – emerging insights into their domain functions, biological roles and disease relevance

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

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