Page 215 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology Tetramethyl thyroxine boosts bladder cancer

by 5 – 28.3% and 4.7 – 18.7%, respectively, following T4 invasive capability. Furthermore, follow-up data from
treatment. Concurrently, the cell migration rates after the some patients showed that those with high integrin
co-incubation of T4 with T24 and EJ-1 cells also exhibited αV expression had higher recurrence rates and shorter
increases of 9.27 – 41.01% and 11.47 – 35.8%, respectively. survival times, suggesting its potential clinical value in
In addition, the apoptosis rates of T24 and EJ-1 cells were prognosis assessment. Integrin αV is highly expressed
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significantly reduced after T4 treatment. In vivo xenograft during angiogenesis and promotes endothelial cell growth
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tumor models further substantiated that T4 promotes BC and survival. In melanoma cells, integrin αV controls
tumor formation in BABLC/C nude mice. cell survival by inactivating p53 and activating the MEK1
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Mechanistically, we found that the mRNA expression signaling pathway. VEGF is a crucial regulator of tumor
of integrin αV and VEGF increased, the expression of angiogenesis, facilitating the development of vascular
TP53 mRNA decreased, and the protein levels also showed networks that supply essential oxygen and nutrients to
consistent changes in BC cells after T4 treatment. Integrin tumor cells. In addition, VEGF can enhance the distant
αV is a cell surface receptor that belongs to the integrin metastasis of tumors by influencing the invasiveness and
family. It can form heterodimers with β1, β3, β5, β6, and migratory capabilities of tumor cells, thereby promoting
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β8, resulting in the formation of Alpha-V class integrins, their entry into the bloodstream and lymphatic system.
which play a significant role in the occurrence and VEGF is a downstream molecule of the MAPK pathway, and
development of tumors. The involvement of integrin αV the activation of the PI3K/AKT pathway can promote the
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in tumor development is multifaceted. It can activate TGF- expression of VEGF. This suggests that T4 may promote
β, a cytokine that is crucial for tumor-associated blood the development of BC by activating the MAPK/ERK or
vessel formation. Furthermore, the activation of integrin PI3K/AKT signaling pathways through binding to integrin
αV can inhibit apoptosis by modulating interactions αV. This points the way for further mechanistic research.
with the extracellular matrix. Existing studies have As a tumor suppressor, TP53 prevents the occurrence
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demonstrated that integrin αV is highly expressed in and progression of tumors by inducing G1 phase arrest
tissues from breast cancer, lung cancer, gastric cancer, in the tumor cell cycle and inhibiting the proliferation
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colorectal cancer, and esophageal adenocarcinoma, of damaged tumor cells. In summary, T4 promotes the
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and it promotes the proliferation, invasion, and migration angiogenesis of BC cells by activating integrin αV. The
of tumor cells. van der Horst et al. found that the high expression of VEGF, an angiogenic factor, supports
knockdown of integrin αV expression in BC cells in vitro this assertion. Concurrently, the increased expression of
significantly reduced cell migration ability. The expression VEGF enhances the migratory capacity of BC cells. In
of the epithelial marker E-cadherin associated with EMT addition, the activation of integrin αV and the inhibition
increased, while the mesenchymal markers N-cadherin of TP53 contribute to the suppression of apoptosis.
and vimentin were downregulated. In addition, the Thyroid hormones can serve as an energy source for
study revealed that the subpopulation of BC cells with intestinal cells by binding to short-chain fatty acids, which
high expression of integrin αV typically exhibited higher are metabolites of anaerobic microbial fermentation,
ALDH activity, with ALDH being a biomarker commonly thereby inducing intestinal cell differentiation.
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used to identify cancer stem cells. When integrin αV was In addition, thyroid hormones can regulate the
knocked down through siRNA, the proportion of ALDH- Wnt/β-catenin signaling pathway through TRα1,
positive cells significantly decreased, and the expression affecting the self-renewal of intestinal stem cells. Thyroid
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levels of stem cell-related transcription factors such as hormones also modulate the proliferation and activation
NANOG and BMI1 were also markedly downregulated. of T lymphocytes by influencing the NF-κB and protein
Furthermore, in the colony formation assay, knockdown kinase C signaling pathways, as well as β-adrenergic
of integrin αV significantly inhibited the self-renewal receptors. It is evident that thyroid hormones exert
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capacity of cells. These results indicated that integrin αV specific effects on the proliferation of normal cells in
not only promotes the metastasis and invasion behaviors of different tissues. By increasing normal urothelial cells
BC cells by regulating the EMT process but may also play a for comparative studies, further investigation into the
regulatory role in maintaining the characteristics of cancer differences in the mechanisms and effect intensities of T4
stem cells. Sachs et al. conducted a clinical evaluation and in normal urothelial cells and BC cells can clarify the tissue
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found that the expression of integrin αV was significantly specificity of T4. In future studies, we could incorporate
elevated in high-grade BC and muscle-invasive carcinoma. multiple BC cell lines (such as J82, 5637, and HT1376)
Particularly, in aggressive tumors, the expression level and primary BC cells to conduct in vivo and in vitro
of integrin αV was positively correlated with the degree experiments, thereby enhancing the generalizability of
of tumor differentiation, proliferative activity, and local the research findings and elucidating the promoting

Volume 9 Issue 2 (2025) 207 doi: 10.36922/EJMO025080037