A Multiomic Analysis Reveals How Breast Cancers Disseminated to the Bone Marrow Acquire Aggressive Phenotypes through Tumor-Stroma Tunnels DOI Open Access
Saptarshi Sinha, Brennan W. Callow, Alex P. Farfel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 21, 2023

Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed recapitulate genes proteins, some borrowed others tumor-intrinsic, induced in by direct contact. Protein-protein interaction networks revealed the rich connectome between 'borrowed' 'intrinsic' components. Bioinformatics prioritized one components,

Language: Английский

MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities DOI Open Access
Khadijeh Mahboobnia, Dianne J. Beveridge, George C. Yeoh

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9393 - 9393

Published: Aug. 29, 2024

Hepatocellular carcinoma (HCC) presents a significant global health burden, with alarming statistics revealing its rising incidence and high mortality rates. Despite advances in medical care, HCC treatment remains challenging due to late-stage diagnosis, limited effective therapeutic options, tumor heterogeneity, drug resistance. MicroRNAs (miRNAs) have attracted substantial attention as key regulators of pathogenesis. These small non-coding RNA molecules play pivotal roles modulating gene expression, implicated various cellular processes relevant cancer development. Understanding the intricate network miRNA-mediated molecular pathways is essential for unraveling complex mechanisms underlying hepatocarcinogenesis developing novel approaches. This manuscript aims provide comprehensive review recent experimental clinical discoveries regarding role miRNAs influencing hallmarks HCC, well their promising utility potential targets.

Language: Английский

Citations

5

A circuit for secretion‐coupled cellular autonomy in multicellular eukaryotic cells DOI Creative Commons
Lingxia Qiao, Saptarshi Sinha, Amer Ali Abd El‐Hafeez

et al.

Molecular Systems Biology, Journal Year: 2023, Volume and Issue: 19(4)

Published: March 1, 2023

Cancers represent complex autonomous systems, displaying self-sufficiency in growth signaling. Autonomous is fueled by a cancer cell's ability to "secrete-and-sense" factors (GFs): poorly understood phenomenon. Using an integrated computational and experimental approach, here we dissect the impact of feedback-coupled GTPase circuit within secretory pathway that imparts secretion-coupled autonomy. The assembled when Ras-superfamily monomeric Arf1, heterotrimeric Giαβγ their corresponding GAPs GEFs are coupled GIV/Girdin, protein known fuel aggressive traits diverse cancers. One forward two key negative feedback loops create closed-loop control, allow GTPases coregulate each other, convert expected switch-like behavior Arf1-dependent secretion into unexpected dose-response alignment sensing secretion. Such translates cell survival self-sustained stimulus-proportionate Proteomic studies protein-protein interaction network analyses pinpoint GFs (e.g., epidermal GF) as stimuli for such self-sustenance. Findings highlight how enhanced coupling biological switches cells critical multiscale control achieve autonomy factors.

Language: Английский

Citations

11

ANTICANCER LIPID-BASED DRUG DELIVERY SYSTEMS: BASIC KNOWLEDGE AND RECENT APPLICATIONS DOI Creative Commons
Mohamed M. Shehata

Nano TransMed, Journal Year: 2024, Volume and Issue: unknown, P. 100054 - 100054

Published: Oct. 1, 2024

Language: Английский

Citations

3

Interlinked switch circuits of biological intelligence DOI Creative Commons
Raktim Mukherjee, Saptarshi Sinha, Gary D. Luker

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(4), P. 286 - 289

Published: Feb. 9, 2024

Eukaryotic cells learn and adapt via unknown network architectures. Recent work demonstrated a circuit of two GTPases used by to overcome growth factor scarcity, encouraging our view that artificial biological intelligence share strikingly similar design principles function as deep reinforcement learning (RL) agents in uncertain environments.

Language: Английский

Citations

0

In vitro evidence for the potential of EGFR inhibitors to decrease the TGF-β1-induced dispersal of circulating tumour cell clusters mediated by EGFR overexpression DOI Creative Commons
Jorian D. Hapeman, Rakshit Galwa, Caroline S. Carneiro

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 28, 2024

Most cancer-related deaths are due to the spread of tumour cells throughout body-a process known as metastasis. While in vasculature, these referred circulating (CTCs) and can be found either single or clusters (often including platelets), with latter having highest metastatic potential. However, biology CTC is poorly understood, there no therapies that specifically target them. We previously developed an vitro model system for proposed a new extravasation involves cluster dissociation, adherence, single-cell invasion response TGF-β1 released by platelets. Here, we investigated TGF-β1-induced gene expression changes this model, focusing on genes which targeted drugs available. In addition upregulation signalling pathway, (i) EGF/EGFR those coding EGFR several ligands, were also induced, (ii) Erlotinib Osimertinib, two therapeutic EGFR/tyrosine kinase inhibitors, decreased adherence cluster-like line despite expressing wild-type EGFR. Overall, suggest inhibitors have potential decrease dispersal respond overexpress (irrespective its status) thus could improve patient survival.

Language: Английский

Citations

0

A Multiomic Analysis Reveals How Breast Cancers Disseminated to the Bone Marrow Acquire Aggressive Phenotypes through Tumor-Stroma Tunnels DOI Open Access
Saptarshi Sinha, Brennan W. Callow, Alex P. Farfel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 21, 2023

Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed recapitulate genes proteins, some borrowed others tumor-intrinsic, induced in by direct contact. Protein-protein interaction networks revealed the rich connectome between 'borrowed' 'intrinsic' components. Bioinformatics prioritized one components,

Language: Английский

Citations

1