HTR1A Inhibits the Progression of Triple‐Negative Breast Cancer via TGF‐β Canonical and Noncanonical Pathways

Abstract

Triple‐negative breast cancer is the most aggressive subtype of breast cancer and the incidence of depression in breast cancer patients is high, which leading to worse survival and increased risk of recurrence. The effect of antidepressants on breast cancer patients remains contradictory, which might be due to variations in antidepression targets. Therefore, there is significant value to explore the antitumor potential of antidepressants and discover new therapeutic targets for breast patients. The authors screen antidepressant‐related oncogenes or suppressors by using siRNAs. After combining functional experiments with online database analysis, 5‐hydroxytryptamine receptor 1A (HTR1A is selected with antitumor potential in breast cancer cells in vivo and in vitro. RNA‐seq analysis and coimmunoprecipitation assays indicate that HTR1A interacts with TRIM21 and PSMD7 to inhibit the degradation of T β RII through the ubiquitin‐proteasome pathway, thereby inhibiting the transforming growth factor‐ β (TGF‐β) canonical and noncanonical pathway. In addition, HTR1A is an independent predictive factor for breast cancer patients. The combined treatment of HTR1A agonists with demethylation drugs may significantly improve patient survival. It is of great significance to clarify the function and mechanism of the depression‐related gene HTR1A in breast cancer, which might provide a new approach for triple‐negative breast cancer patients.

AEBP1 Contributes to Breast Cancer Progression by Facilitating Cell Proliferation, Migration, Invasion, and Blocking Apoptosis

“…To resolve which tumor-related signaling pathway played a key role by AEBP1 in BCa progression, the UniProt dataset was utilized and it was found that AEBP1 can interact with NF-κB, MAPK1/3 and PTEN (phosphatase and tensin homolog deleted on chromosome 10), which is also supported by the previous publications [17][18][19]. On the other hand, the TGF-β signaling pathway plays an indispensable role in the progression of BCa [20]. Western blotting was performed to measure the protein levels of p-Smad2, p-Smad3, Smad2/3, PTEN, p-AKT, AKT, p-NF-κB, NF-κB, p-ERK and ERK.…”

G protein-coupled Receptor Contributions to Wing Growth and Morphogenesis inDrosophila melanogaster

“…For example, knockdown of 5-HT1B, Rh2, CCHa1-R , and fz in the developing Drosophila wing produced vein thickening phenotypes. The human orthologs for these genes, HTR1A, OPN4, GRPR , and FZD7 , respectively, have disease manifestations that increase metastasis, tumor cell growth, cell migration, and endothelial cell proliferation (Table 1) (Liu et al . 2022a; de Assis et al .…”

“…For example, knockdown of 5-HT1B, Rh2, CCHa1-R, and fz in the developing Drosophila wing produced vein thickening phenotypes. The human orthologs for these genes, HTR1A, OPN4, GRPR, and FZD7, respectively, have disease manifestations that increase metastasis, tumor cell growth, cell migration, and endothelial cell proliferation (Table 1) (Liu et al 2022a;de Assis et al 2021;Patel et al 2014;Zhang and Xu 2022). Similar vein thickening defects have been observed when knocking down the dSTIM gene, a calcium release-activated calcium (CRAC) channel (Eid et al 2008).…”

Biomimetic Nanovehicle-Enabled Targeted Depletion of Intratumoral Fusobacterium nucleatum Synergizes with PD-L1 Blockade against Breast Cancer

“…Breast cancer has surpassed lung cancer as the most common malignancy in the world . In particular, triple-negative breast cancer (TNBC) is the most challenging subtype of BC due to its high risk of recurrence and poor outcome. , With the success of tumor immunotherapy, BC has also entered an era of immunotherapy. The US Food and Drug Administration (FDA) has approved Atezolizumab and Keytruda for use in unresectable high-risk early, locally advanced, and metastatic TNBC. , Despite high mutation frequencies and PD-L1 expression in these subtypes, most patients remain unresponsive to ICB. , For instance, the response rate of PD-1 blockade in 170 patients with metastatic TNBC was only 4.7% .…”

“…1 In particular, triplenegative breast cancer (TNBC) is the most challenging subtype of BC due to its high risk of recurrence and poor outcome. 2,3 With the success of tumor immunotherapy, BC has also entered an era of immunotherapy. The US Food and Drug Administration (FDA) has approved Atezolizumab and Keytruda for use in unresectable high-risk early, locally advanced, and metastatic TNBC.…”