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Last update 23 Jan 2025

TM4SF4

Last update 23 Jan 2025

Basic Info

Synonyms

il-TMP, ILTMP, Intestine and liver tetraspan membrane protein

+ [3]

Introduction

Regulates the adhesive and proliferative status of intestinal epithelial cells. Can mediate density-dependent cell proliferation.

Drugs associated with TM4SF4

AGK-102

Target

TM4SF4

Mechanism

TM4SF4 inhibitors

Active Org.

Algok Bio, Inc.

Originator Org.

Algok Bio, Inc.

Active Indication

Liver Cancer [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ECL-2B7

Target

TM4SF4

Mechanism

TM4SF4 inhibitors

Active Org.

Algok Bio, Inc.

Originator Org.

Algok Bio, Inc.

Active Indication

Non-Small Cell Lung Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

WO2022265439

Patent Mining

Target

TM4SF4

Mechanism-

Active Org.

Korea Atomic Energy Research Institute [+1]

Originator Org.

Sejong University Industry Academy Cooperation Foundation [+1]

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TM4SF4

100 Translational Medicine associated with TM4SF4

0 Patents (Medical) associated with TM4SF4

Literatures (Medical) associated with TM4SF4

31 Dec 2024·Cancer Biology & Therapy

TM4SF4 is a diagnostic biomarker accelerating progression of papillary thyroid cancer via AKT pathway

Article

Author: Lin, Lizhi ; Xu, Tiansheng ; Si, Yuhao ; Wen, Jialiang

The incidence of papillary thyroid cancer (PTC) has been steadily rising, though the underlying mechanism remains unclear. This study aims to elucidate the biological role of TM4SF4 in the PTC progression. Our differential expression analysis indicated that TM4SF4 was significantly upregulated in PTC, which was corroborated in both our local cohort and the data from Human Protein Atlas. Additionally, clinical characteristics analysis and receiver operating characteristic curves (ROC) demonstrated that TM4SF4 served as a significant diagnostic marker for PTC. Correlation and enrichment analysis of TM4SF4-related partners suggested that it was involved in cell junction and cohesion processes. Furthermore, immune infiltration analysis revealed a positive correlation between TM4SF4 expression and the immune activation in PTC. Importantly, in vitro experiments demonstrated that TM4SF4 downregulation suppressed the proliferation and metastasis of PTC cell lines while inducing apoptosis. We further discovered that the AKT activator SC79 was able to reverse the malignant behaviors suppression caused by TM4SF4 knockdown, suggesting that TM4SF4 may promote PTC progression via the AKT pathway. In conclusion, our study highlights the oncogenic role of TM4SF4 in PTC and identifies it as a novel biomarker for diagnosis and treatment.

01 Dec 2024·Functional & Integrative Genomics

Integration of osimertinib-targeted EGFR gene-associated differential gene expression in constructing a prognostic model for lung adenocarcinoma

Article

Author: Yang, Quan ; Su, Wenmei ; Yu, Lili ; Li, Haiwen ; Yang, Li ; Liang, Zhu

Lung adenocarcinoma (LUAD) is one of the deadliest cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy is an important approach for treating LUAD. However, the development of acquired resistance poses a serious clinical challenge. Our objective was to explore the differentially expressed genes (DEGs) associated with EGFR and detect biomarkers for diagnosing and treating osimertinib resistance in LUAD patients. LUAD datasets were downloaded from public databases. Differential expression analysis was performed to screen DEGs, and prognostic modules were constructed by Cox regression. Enrichment analysis, gene regulatory network analysis and immune microenvironment analysis were employed to explore the underlying mechanisms in LUAD. Finally, the expression of prognosis module genes (PMGs) was validated in 8 LUAD tissue specimens and 5 cell lines by qRT-PCR. In total, 13 differential module genes (BIRC3, CCT6A, CPLX2, GLCCI1, GSTA1, HLA-DQB2, ID1, KCTD12, MUC15, NOTUM, NT5E, TCIM, and TM4SF4) were screened for the construction of a prognostic module. Notably, CCT6A and KCTD12 demonstrated excellent accuracy in the diagnosis of LUAD. Immune dysregulation and BIRC3, HLA-DQB2, KCTD12, and NT5E expression were significantly associated with invasive immune cells in LUAD patients. The expression level of CCT6A was highest in PC9-OR and H1975-OR cells, while the expression level of KCTD12 was highest in paracancerous tissue and HBE cells. The constructed prognostic model showed promise in predicting the survival of LUAD patients. Notably, KCTD12 and CCT6A might be candidate biomarkers for improving diagnostic performance and guiding individualized therapy for EGFR-TKI-resistant LUAD patients.

02 Aug 2023·European Journal of Endocrinology

Genetic determinants of thyroid function in children

Article

Author: Korevaar, Tim I M ; Jaddoe, Vincent V W ; Dayan, Colin ; Walsh, John P ; Wilson, Scott G ; Campbell, Purdey J ; Peeters, Robin P ; Tiemeier, Henning ; Taylor, Peter N ; Martin, Nicholas G ; Medici, Marco ; Mulder, Tessa A

AbstractObjectiveGenome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children.MethodsWe selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects.ResultsIn childhood, 30/60 SNPs were associated with TSH and 11/31 SNPs with FT4 after multiple testing correction. The effect sizes for AADAT, GLIS3, TM4SF4, and VEGFA were notably larger than in adults. The TSH PRS explained 5.3%-8.4% of the variability in TSH concentrations; the FT4 PRS explained 1.5%-4.2% of the variability in FT4 concentrations. Five TSH SNPs and no FT4 SNPs were associated with thyroid function in neonates.ConclusionsThe effects of many known thyroid function SNPs are already apparent in childhood and some might be notably larger in children as compared to adults. These findings provide new knowledge about genetic regulation of thyroid function in early life.

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TM4SF4

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