Autocrine Signaling and Quorum Sensing: Extreme Ends of a Common Spectrum

Doğaner, Berkalp A.; Yan, Lawrence K.Q.; Youk, Hyun

doi:10.1016/j.tcb.2015.11.002

Cited by 77 publications

(84 citation statements)

References 72 publications

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“…These can include resistance to signals that inhibit cell multiplication [1–4], growth factor independence [5, 6], a decrease in programmed cell death [7–9], self-signaling to stimulate cell multiplication [10–13], invasiveness and metastasis [14], tumorigenesis in animal models [15–17], and a number of additional characteristics [1, 2]. Recently, we demonstrated that tumorigenic cell lines derived from breast tumors, but not non-tumorigenic cell lines, also possess the capacity to generate large cell aggregates in a 3D Matrigel model through coalescence of clonal aggregates formed through the multiplication of single cells seeded in the gel [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44

et al. 2017

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Using unique computer-assisted 3D reconstruction software, it was previously demonstrated that tumorigenic cell lines derived from breast tumors, when seeded in a 3D Matrigel model, grew as clonal aggregates which, after approximately 100 hours, underwent coalescence mediated by specialized cells, eventually forming a highly structured large spheroid. Non-tumorigenic cells did not undergo coalescence. Because histological sections of melanomas forming in patients suggest that melanoma cells migrate and coalesce to form tumors, we tested whether they also underwent coalescence in a 3D Matrigel model. Melanoma cells exiting fragments of three independent melanomas or from secondary cultures derived from them, and cells from the melanoma line HTB-66, all underwent coalescence mediated by specialized cells in the 3D model. Normal melanocytes did not. However, coalescence of melanoma cells differed from that of breast-derived tumorigenic cell lines in that they 1) coalesced immediately, 2) underwent coalescence as individual cells as well as aggregates, 3) underwent coalescence far faster and 4) ultimately formed long, flat, fenestrated aggregates that were extremely dynamic. A screen of 51 purified monoclonal antibodies (mAbs) targeting cell surface-associated molecules revealed that two mAbs, anti-beta 1 integrin/(CD29) and anti-CD44, blocked melanoma cell coalescence. They also blocked coalescence of tumorigenic cells derived from a breast tumor. These results add weight to the commonality of coalescence as a characteristic of tumorigenic cells, as well as the usefulness of the 3D Matrigel model and software for both investigating the mechanisms regulating tumorigenesis and screening for potential anti-tumorigenesis mAbs.

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Section: Introductionmentioning

confidence: 99%

Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44

et al. 2017

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“…Cell-cell communication in multi-cellular organism can be mediated by autocrine signaling, paracrine signaling and juxtacrine signaling (contact-mediated signaling). There is a fundamental trade-off between autocrine and paracrine signaling 28 . The former enables a single cell to talk to itself whereas the latter is designed to allow multiple cell types to talk to each other.…”

Section: Crosstalk Score Of a Ligand-receptor Pair Between Two Cell Tmentioning

confidence: 99%

CytoTalk:De novoconstruction of signal transduction networks using single-cell RNA-Seq data

Peng

Gao

et al. 2020

Preprint

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Single-cell technology has opened the door for studying signal transduction in a complex tissue at unprecedented resolution. However, there is a lack of analytical methods for de novo construction of signal transduction pathways using single-cell omics data. Here we present CytoTalk, a computational method for de novo constructing cell type-specific signal transduction networks using single-cell RNA-Seq data. CytoTalk first constructs intracellular and intercellular gene-gene interaction networks using an information-theoretic measure between two cell types. Candidate signal transduction pathways in the integrated network are identified using the prizecollecting Steiner forest algorithm. We applied CytoTalk to a single-cell RNA-Seq data set on mouse visual cortex and evaluated predictions using high-throughput spatial transcriptomics data generated from the same tissue. Compared to published methods, genes in our inferred signaling pathways have significantly higher spatial expression correlation only in cells that are spatially closer to each other, suggesting improved accuracy of CytoTalk. Furthermore, using single-cell RNA-Seq data with receptor gene perturbation, we found that predicted pathways are enriched for differentially expressed genes between the receptor knockout and wild type cells, further validating the accuracy of CytoTalk. In summary, CytoTalk enables de novo construction of signal transduction pathways and facilitates comparative analysis of these pathways across tissues and conditions.

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“…Other environmental factors such as pH, oxygen, phosphate and diffusibility of the growth medium also influence competence development (Chen and Morrison, 1987;Claverys et al, 2002;Echenique et al, 2000;Yang et al, 2010). Thus, the initiation of competence can be considered as a combination of diffusion sensing and autocrine-like signaling (Doğaner et al, 2016;Moreno-Gámez et al, 2017). The competent state is activated in response to several antibiotics, which thereby allow the bacterium to take up foreign DNA and potentially acquire antimicrobial resistance determinants (Prudhomme et al, 2006;Slager et al, 2014;Stevens et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Antibiotic-induced cell chaining triggers pneumococcal competence by reshaping quorum sensing to autocrine signaling

Domenech

Slager

Veening

2018

Preprint

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Streptococcus pneumoniae can acquire antibiotic resistance by activation of competence and subsequent DNA uptake. Here, we demonstrate that aztreonam (ATM) and clavulanic acid (CLA) promote competence. We show that both compounds induce cell chain formation by targeting the D,D-carboxypeptidase PBP3. In support of the hypothesis that chain formation promotes competence, we demonstrate that an autolysin mutant (ΔlytB) is hypercompetent. Since competence is initiated by the binding of a small extracellular peptide (CSP) to a membrane-anchored receptor (ComD), we wondered if chain formation alters CSP diffusion kinetics. Indeed, the presence of ATM or CLA affects competence synchronization by shifting from global to local quorum sensing, as CSP is primarily retained to chained cells, rather than shared in a common pool. Importantly, autocrine-like signaling prolongs the time-window in which the population is able to transform. Together, these insights demonstrate the versatility of quorum sensing and highlight the importance of an accurate antibiotic prescription.

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Autocrine Signaling and Quorum Sensing: Extreme Ends of a Common Spectrum

Cited by 77 publications

References 72 publications

Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44

Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44

CytoTalk:De novoconstruction of signal transduction networks using single-cell RNA-Seq data

Antibiotic-induced cell chaining triggers pneumococcal competence by reshaping quorum sensing to autocrine signaling

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