IQGAP scaffold proteins are the multifunctional regulators of cellular signaling and malignant transformation

Сковородникова, П. А.; Chesnokov, Mikhail Shakirovich; Будко, А. А.; Кустова, И. Ф.; Лазаревич, Н. Л.

doi:10.17650/2313-805x-2017-4-2-36-45

Cited by 3 publications

(2 citation statements)

References 50 publications

(134 reference statements)

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“…IQGAP family of proteins regulates intracellular signaling, cell proliferation, and migration is involved in the processes of cytokinesis and vesicle transport. Another function of IQGAP proteins is to participate in the formation of intercellular contacts in epithelial tissues [18]. Overexpression of GPR161 reduces serine phosphorylation of IQGAP1, which corresponds to the observed activation of mTORC1 [17].…”

Section: Introductionmentioning

confidence: 94%

Gpr161 Receptor as a Novel Target for Antibody-Based Immunotherapy of Triple-Negative Breast Cancer

Mukanov¹,

Mukantayev²,

Tarlykov³

2018

Eurasian Journal of Applied Biotechnology

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Triple-negative breast cancer is a rare type of breast cancer, accounting for 20% of all women diagnosed with the adenocarcinoma. Triple-negative breast cancer cells are mainly characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptors. Moreover, these cells do not respond to hormonal and targeted treatment with monoclonal antibodies. A literature review revealed several receptors in the oncogenic cells of this phenotype with potential to serve as a novel target for therapy. In particular, the G-protein coupled receptor (GPR) 161 was found to be overexpressed in triple-negative breast cancer cells, and correlated with a poor prognosis of the disease. In addition, overexpression of GPR161 in human mammary epithelial cells resulted in increased cell proliferation, migration, intracellular accumulation of E-cadherin, and the formation of multiple structures in a three-dimensional cell culture. Activation of the receptor reduces the phosphorylation of GTPase-activating protein 1 proteins, thereby enhancing mammalian target of rapamycin signaling pathways. GPCRs belong to a family of cell membrane proteins that transform extracellular signals into intracellular signaling pathways. These receptors play a key role in many important physiological processes whose malfunction may lead to various diseases, including cancer. Several currently produced drugs target different members of the GPCR family and have shown excellent therapeutic advantages. Therefore, huge efforts are focused on developing new drugs based on GPCRs, particularly for the treatment of cancer. This article provides an overview of data that show great promise in new opportunities for the treatment of triple-negative breast cancer. In particular, research on GPCRs is highlighted as promising targets for monoclonal antibodies and, after humanization, as therapeutic drugs

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Section: Introductionmentioning

confidence: 94%

Gpr161 Receptor as a Novel Target for Antibody-Based Immunotherapy of Triple-Negative Breast Cancer

Mukanov¹,

Mukantayev²,

Tarlykov³

2018

Eurasian Journal of Applied Biotechnology

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“…GPR161 receptor, like all receptors of this family, transforms the signals of extracellular ligands across the plasma membrane, modulating the intracellular signaling pathways. The receptor is involved in the activation of the mTORC1/S6K signaling pathway by reducing the phosphorylation of IQGAP1 [6].…”

Section: Introductionmentioning

confidence: 99%

Obtaining Recombinant Extracellular Fragments of Gpr161 Receptor

Kanaev¹,

Mukanov²,

Adish³

et al. 2019

Eurasian Journal of Applied Biotechnology

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The GPR161 is a receptor of the GPCR family and identified as a prognostic biomarker for triple negative breast cancer (TNBC). TNBC characterized by lack of expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor (Her2), early recurrence and poor prognosis. The GPR161 is an important regulator of the proliferation and migration of cancer cells. However, anti-GPCR receptor drugs are rarely used in the treatment of cancer, despite evidence of receptor involvement in various aspects of cancer development. Upon receipt of monoclonal antibodies, the success of the study is associated with the presence in sufficient quantities of pure antigen preparations. Recently, gene synthesis under de novo conditions has become a powerful tool in biotechnology. A number of methods have been described, representing thermodynamic balanced methods based on polymerase chain reaction (PCR). This paper presents the results of gene synthesis and the preparation of a recombinant extracellular fragment of the receptor. To obtain a recombinant protein, an area located outside the cell membrane between the 4th and 5th helix of the receptor was selected. A genetic construct based on the pET32 vector carrying the extracellular fragment of the human GPR161 receptor has been developed and obtained. Strain Escherichia coli BL21/pET32/TM4-5GPR161 producing recombinant extracellular fragment rTM4-5 GPR161 was obtained. The conditions for the isolation and purification of recombinant protein were determined, and its immunogenic properties were studied. Purified recombinant protein TM4-5GPR161 in its immunological characteristics suitable for the production of strains of hybrid cells producing monoclonal antibodies to the GPR161 receptor.

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