Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance

Rahim, Nur Syafiqah; Wu, Yuan Seng; Sim, Maw Shin; Velaga, Appalaraju; Bonam, Srinivasa Reddy; Gopinath, Subash C. B.; Subramaniyan, Vetriselvan; Choy, Ker Woon; Teow, Sin-Yeang; Fareez, Ismail M.; Samudi, Chandramathi; Sekaran, Shamala Devi; Sekar, Mahendran; Guad, Rhanye Mac

doi:10.3390/ph16010110

Cited by 7 publications

(4 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have revealed the underlying mechanism by which TM4SFs are involved in the malignant progression of cancers [5,36]. To further investigate the underlying mechanism responsible for TM4SF family member regulation, we performed gene enrichment analysis of the core genes (protein interactions, co-expressed genes) potentially correlated with TM4SF function.…”

Section: Discussionmentioning

confidence: 99%

Integrated multi-omics analyses reveal the TM4SF family genes with prognostic and therapeutic relevance in hepatocellular carcinoma

Tang,

Wang,

et al. 2024

Aging

View full text Add to dashboard Cite

TM4SF family members (TM4SFs) have been shown to be aberrantly expressed in multiple types of cancer. However, a comprehensive investigation of the TM4SFs has yet to be performed in LIHC. The study comprehensively investigated the expression and prognostic value of TM4SFs. Then, a TM4SFs-based risk model and nomogram were constructed for prognostic prediction. Finally, functional loss of TM4SFs was performed to verify the potential role of TM4SFs in LIHC. We found that TM4SFs were significantly up-regulated in LIHC. High expression and hypomethylation of TM4SFs were associated with poor prognosis of LIHC patients. Then, a TM4SFs-based risk model was constructed that could effectively classify LIHC patients into high and low-risk groups. In addition, we constructed a prognostic nomogram that could predict the long-term survival of LIHC patients. Based on immune infiltration analysis, high-risk patients had a relatively higher immune status than low-risk patients. Moreover, the prediction module could predict patient responses to immunotherapy and chemotherapy. Finally, loss-of-function studies showed that TM4SF4 knockdown could substantially suppress the growth, migratory, and invasive abilities of LIHC cells. Targeting TM4SFs will contribute to effective immunotherapy strategies and improve the prognosis of liver cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated multi-omics analyses reveal the TM4SF family genes with prognostic and therapeutic relevance in hepatocellular carcinoma

Tang,

Wang,

et al. 2024

Aging

View full text Add to dashboard Cite

show abstract

“…The overexpression of TM4SF5, a protein, is a crucial factor in encouraging the proliferation of tumor cells and is consistently found in hepatocarcinoma patients, contributing to hightened expression of TM4SF5 connected to VEGF level and angiogenesis [217]. During TM4SF5-induced multilayer growth, TM4SF5 activates FAK by increasing phosphorylation at Tyr577 (pY577FAK) and enhances the expression and stability of p27Kip1 in the cytosol.…”

Section: Chalconesmentioning

confidence: 99%

Flavonoids with Anti-Angiogenesis Function in Cancer

Wei,

Zhang

2024

Molecules

View full text Add to dashboard Cite

The formation of new blood vessels, known as angiogenesis, significantly impacts the development of multiple types of cancer. Consequently, researchers have focused on targeting this process to prevent and treat numerous disorders. However, most existing anti-angiogenic treatments rely on synthetic compounds and humanized monoclonal antibodies, often expensive or toxic, restricting patient access to these therapies. Hence, the pursuit of discovering new, affordable, less toxic, and efficient anti-angiogenic compounds is imperative. Numerous studies propose that natural plant-derived products exhibit these sought-after characteristics. The objective of this review is to delve into the anti-angiogenic properties exhibited by naturally derived flavonoids from plants, along with their underlying molecular mechanisms of action. Additionally, we summarize the structure, classification, and the relationship between flavonoids with their signaling pathways in plants as anti-angiogenic agents, including main HIF-1α/VEGF/VEGFR2/PI3K/AKT, Wnt/β-catenin, JNK1/STAT3, and MAPK/AP-1 pathways. Nonetheless, further research and innovative approaches are required to enhance their bioavailability for clinical application.

show abstract

“…Rsu1 interacts indirectly with integrin beta-1 via the PINCH/ILK complex, ultimately inhibiting NF-κB. Tm4sf1 interacts constitutively with integrin beta-1 (Shih et al, 2009) and can promote AKT phosphorylation (Rahim et al, 2023).…”

Section: Integrated Analysis Identifies a Subset Of Genes Related To ...mentioning

confidence: 99%

Protein Kinase A Inhibition Epigenetically SilencesRen1

Smith,

Paxton,

Medrano

et al. 2023

Preprint

View full text Add to dashboard Cite

Rationale: Renin-expressing cells are myoendocrine cells crucial for survival which detect changes in blood pressure and release renin to maintain homeostasis. One of the pathways responsible for renin expression includes cAMP as a central factor. cAMP binds to subunits of protein kinase A (PKA), ultimately recruiting both CBP and p300. Binding to the cAMP-responsive element in the renin enhancer region thus amplifies renin transcription. Objective: To evaluate transcriptomic and epigenomic changes occurring at the renin locus via cAMP pathway inhibition. Methods and Results: We treated As4.1 cells (a tumoral cell line that constitutively expresses renin) with the PKA inhibitor H89 (treated) or DMSO (control). We then performed independent ATAC-seq, scRNA-seq, and ChIP-seq for H3K27Ac and P300 binding on biological replicates of treated and control As4.1 cells. Ren1 expression is significantly reduced following PKA inhibition with a corresponding loss in H3K27Ac and P300 binding at the locus. A restricted set of 9 genes with overlapping dynamically accessible regions, differential gene expression, and H3K27Ac and P300 binding were identified with roles among three primary renin regulatory paradigms. Conclusions: The data suggests that cAMP pathway inhibition controls renin expression through a reduction not in accessibility alone, but via a switch from an active to poised state of epigenetic control, a shift towards a less differentiated cellular identity, and the disruption of not only cAMP, but baroreceptor and Notch mediated renin regulatory pathways.

show abstract

Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance

Cited by 7 publications

References 141 publications

Integrated multi-omics analyses reveal the TM4SF family genes with prognostic and therapeutic relevance in hepatocellular carcinoma

Integrated multi-omics analyses reveal the TM4SF family genes with prognostic and therapeutic relevance in hepatocellular carcinoma

Flavonoids with Anti-Angiogenesis Function in Cancer

Protein Kinase A Inhibition Epigenetically SilencesRen1

Contact Info

Product

Resources

About