Molecular Basis of LH Action on Breast Cancer Cell Migration and Invasion via Kinase and Scaffold Proteins

Mondaca, Joselina Magali; Uzair, Ivonne Denise; Guijarro, Ana Carla Castro; Flamini, Marina Inés; Sanchez, Angel Matías

doi:10.3389/fcell.2020.630147

Cited by 4 publications

(3 citation statements)

References 60 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, preliminary data point to a potential function for LH in tumorigenesis. This hormone controls cell migration and invasion in BC cells that exhibit functional LH receptors (LHR) [ 22 ].…”

Section: Reviewmentioning

confidence: 99%

Predisposing and Overall Effects of Reproductive Hormones on Breast Cancer: A Review

Sarda,

Jogdand

2023

Cureus

View full text Add to dashboard Cite

Cancer, the second leading cause of mortality worldwide, has been the subject of extensive and quickly changing scientific study and practice. Cancer remains a mystery despite the enormous effort put into understanding the genesis of cancerous cells, the development of malignant tissues, and the process by which they propagate and recur. Cells from humans that have been recruited by cancer and, to some extent, changed into pathogenic organisms or the foundation of tumors serve as agents of destruction. Understanding cancers leads to challenging philosophical issues since they undermine and use multicellular organization processes. Cancer metastasizing cells adopt new phenotypes while discarding previous behaviors. The absence of comprehensive knowledge of this has hampered the development of therapeutics for metastatic illness. For systems-level experimental and computational metastasis modeling, integrating these complex and interconnected features continues to be a problem because metastasis has typically been studied in separate physiological compartments. Lung, breast, and prostate cancers accounted for the bulk of the 18 million new cases of cancer that were diagnosed in 2018. The most frequent cancer in women is breast cancer. Animal experimentation plays a significant role in primary and translational breast cancer research. In theory, such breast cancer models should be comparable to breast cancer in humans in terms of tumor etiology, biological behavior, pathology, and treatment response.

show abstract

Section: Reviewmentioning

confidence: 99%

Predisposing and Overall Effects of Reproductive Hormones on Breast Cancer: A Review

Sarda,

Jogdand

2023

Cureus

View full text Add to dashboard Cite

show abstract

“…This process is initiated through rapid extragonadal LHCGR signalling to Src/ FAK/paxillin resulting in the phosphorylation/activation of the nucleation promoter factors cortactin and N-WASP. As a result, there is an increase in cell motility and the invasive properties which promote the tumour cell metastatic dissemination 60 .…”

Section: Lhcgr Expression In Cancermentioning

confidence: 99%

Gonadotropin Receptor Cross-Talk and Altered Functions in Gonadal and Non-Gonadal Tissues

Singh,

Pathak

2023

JER

View full text Add to dashboard Cite

Reproduction depends on the responses of gonadotropins through their specific receptors. The gonadotropin family has three members; Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Human Chorionic Gonadotropin (hCG). These glycoprotein hormones comprise two subunits, an identical α-subunit and a hormone-specific-β subunit. Their cognate receptors (FSHR and LHCGR) are two adrenergic receptor-like family A/rhodopsin-like G-Protein Coupled Receptors (GPCRs) with structurally distinct ligand binding domains. The hCG binds to LHCGR but has a longer half-life and higher affinity to LHCGR. The expression of FSHR and LHCGR is observed in both gonadal and nongonadal cells. In this review, we will be emphasizing the differential expression of gonadotropin receptors in different cells of the human body, their specific responses through cross-talk, and how a defect in the expression and activity of FSHR and LHCGR may alter the responses of FSH and LH/hCG leading to diseases like PCOS, cancer and metabolic disorders.

show abstract

“…In general, ARPs have numerous crucial biological functions, involving regulation of cell differentiation, migration, adhesion, as well as cargo transport [22,23]. Recent studies have demonstrated that ARPs are associated with malignant behavior in colorectal, breast and lung cancers and that they act in promoting cancer cell invasion and metastasis [24][25][26][27][28][29]. Liu et al recently discovered that ARPC1B in macrophages promoted motility and epithelial-mesenchymal transition (EMT) of glioma cells [30].…”

Section: Introductionmentioning

confidence: 99%

ARPC1B promotes mesenchymal phenotype maintenance and radiotherapy resistance by blocking TRIM21-mediated degradation of IFI16 and HuR in glioma stem cells

Gao

Yang

et al. 2022

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Intratumoral heterogeneity is the primary challenge in the treatment of glioblastoma (GBM). The presence of glioma stem cells (GSCs) and their conversion between different molecular phenotypes contribute to the complexity of heterogeneity, culminating in preferential resistance to radiotherapy. ARP2/3 (actin-related protein-2/3) complexes (ARPs) are associated with cancer migration, invasion and differentiation, while the implications of ARPs in the phenotype and resistance to radiotherapy of GSCs remain unclear. Methods We screened the expression of ARPs in TCGA-GBM and CGGA-GBM databases. Tumor sphere formation assays and limiting dilution assays were applied to assess the implications of ARPC1B in tumorigenesis. Apoptosis, comet, γ-H2AX immunofluorescence (IF), and cell cycle distribution assays were used to evaluate the effect of ARPC1B on radiotherapy resistance. Immunoprecipitation (IP) and mass spectrometry analysis were used to detect ARPC1B-interacting proteins. Immune blot assays were performed to evaluate protein ubiquitination, and deletion mutant constructs were designed to determine the binding sites of protein interactions. The Spearman correlation algorithm was performed to screen for drugs that indicated cell sensitivity by the expression of ARPC1B. An intracranial xenograft GSC mouse model was used to investigate the role of ARPC1B in vivo. Results We concluded that ARPC1B was significantly upregulated in MES-GBM/GSCs and was correlated with a poor prognosis. Both in vitro and in vivo assays indicated that knockdown of ARPC1B in MES-GSCs reduced tumorigenicity and resistance to IR treatment, whereas overexpression of ARPC1B in PN-GSCs exhibited the opposite effects. Mechanistically, ARPC1B interacted with IFI16 and HuR to maintain protein stability. In detail, the Pyrin of IFI16 and RRM2 of HuR were implicated in binding to ARPC1B, which counteracted TRIM21-mediated degradation of ubiquitination to IFI16 and HuR. Additionally, the function of ARPC1B was dependent on IFI16-induced activation of NF-κB pathway and HuR-induced activation of STAT3 pathway. Finally, we screened AZD6738, an ataxia telangiectasia mutated and rad3-related (ATR) inhibitor, based on the expression of ARPC1B. In addition to ARPC1B expression reflecting cellular sensitivity to AZD6738, the combination of AZD6738 and radiotherapy exhibited potent antitumor effects both in vitro and in vivo. Conclusion ARPC1B promoted MES phenotype maintenance and radiotherapy resistance by inhibiting TRIM21-mediated degradation of IFI16 and HuR, thereby activating the NF-κB and STAT3 signaling pathways, respectively. AZD6738, identified based on ARPC1B expression, exhibited excellent anti-GSC activity in combination with radiotherapy.

show abstract

Molecular Basis of LH Action on Breast Cancer Cell Migration and Invasion via Kinase and Scaffold Proteins

Cited by 4 publications

References 60 publications

Predisposing and Overall Effects of Reproductive Hormones on Breast Cancer: A Review

Predisposing and Overall Effects of Reproductive Hormones on Breast Cancer: A Review

Gonadotropin Receptor Cross-Talk and Altered Functions in Gonadal and Non-Gonadal Tissues

ARPC1B promotes mesenchymal phenotype maintenance and radiotherapy resistance by blocking TRIM21-mediated degradation of IFI16 and HuR in glioma stem cells

Contact Info

Product

Resources

About