Rapid Actions of the Nuclear Progesterone Receptor Through CSrc in Cancer

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Jun 24

PMID 35741094

Authors

Claudia Bello-Alvarez

Carmen J Zamora-Sanchez

Ignacio Camacho-Arroyo

Affiliations

Soon will be listed here.

Abstract

The nuclear progesterone receptor (PR) is mainly known for its role as a ligand-regulated transcription factor. However, in the last ten years, this receptor's extranuclear or rapid actions have gained importance in the context of physiological and pathophysiological conditions such as cancer. The PR's polyproline (PXPP) motif allows protein-protein interaction through SH3 domains of several cytoplasmatic proteins, including the Src family kinases (SFKs). Among members of this family, cSrc is the most well-characterized protein in the scenario of rapid actions of the PR in cancer. Studies in breast cancer have provided the most detailed information on the signaling and effects triggered by the cSrc-PR interaction. Nevertheless, the study of this phenomenon and its consequences has been underestimated in other types of malignancies, especially those not associated with the reproductive system, such as glioblastomas (GBs). This review will provide a detailed analysis of the impact of the PR-cSrc interplay in the progression of some non-reproductive cancers, particularly, in GBs.

Citing Articles

Neurosteroids in Glioma: A Novel Therapeutic Concept.

Hogan A, Mut M Life (Basel). 2024; 14(8).

PMID: 39202716 PMC: 11355226. DOI: 10.3390/life14080975.

Role of c-Src in Carcinogenesis and Drug Resistance.

Raji L, Tetteh A, Amin A Cancers (Basel). 2024; 16(1).

PMID: 38201459 PMC: 10778207. DOI: 10.3390/cancers16010032.

Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model.

Abramicheva P, Semenovich D, Zorova L, Pevzner I, Sokolov I, Popkov V Sci Rep. 2023; 13(1):12871.

PMID: 37553369 PMC: 10409855. DOI: 10.1038/s41598-023-39848-2.

Allopregnanolone: Metabolism, Mechanisms of Action, and Its Role in Cancer.

Zamora-Sanchez C, Camacho-Arroyo I Int J Mol Sci. 2023; 24(1).

PMID: 36614002 PMC: 9820109. DOI: 10.3390/ijms24010560.

Applications of nanomaterials for gastrointestinal tumors: A review.

Kanaoujiya R, Porwal D, Srivastava S Front Med Technol. 2022; 4:997123.

PMID: 36119898 PMC: 9475177. DOI: 10.3389/fmedt.2022.997123.

References

Bello-Alvarez C, Del Moral-Morales A, Gonzalez-Arenas A, Camacho-Arroyo I . Intracellular Progesterone Receptor and cSrc Protein Working Together to Regulate the Activity of Proteins Involved in Migration and Invasion of Human Glioblastoma Cells. Front Endocrinol (Lausanne). 2021; 12:640298. PMC: 8032993. DOI: 10.3389/fendo.2021.640298. View

Weissenberger J, Steinbach J, Malin G, Spada S, Rulicke T, Aguzzi A . Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene. 1997; 14(17):2005-13. DOI: 10.1038/sj.onc.1201168. View

Yu H, Chen J, Feng S, Dalgarno D, Brauer A, Schreiber S . Structural basis for the binding of proline-rich peptides to SH3 domains. Cell. 1994; 76(5):933-45. DOI: 10.1016/0092-8674(94)90367-0. View

Wang H, Lee W . Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration. Sci Rep. 2016; 6:31509. PMC: 4980668. DOI: 10.1038/srep31509. View

Feng S, Chen J, Yu H, Simon J, Schreiber S . Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions. Science. 1994; 266(5188):1241-7. DOI: 10.1126/science.7526465. View

Arcos-Montoya D, Wegman-Ostrosky T, Mejia-Perez S, De La Fuente-Granada M, Camacho-Arroyo I, Garcia-Carranca A . Progesterone Receptor Together with PKCα Expression as Prognostic Factors for Astrocytomas Malignancy. Onco Targets Ther. 2021; 14:3757-3768. PMC: 8217595. DOI: 10.2147/OTT.S280314. View

Brown A, Zondlo N . A propensity scale for type II polyproline helices (PPII): aromatic amino acids in proline-rich sequences strongly disfavor PPII due to proline-aromatic interactions. Biochemistry. 2012; 51(25):5041-51. DOI: 10.1021/bi3002924. View

Kuo C, Lee W . Progesterone receptor activation is required for folic acid-induced anti-proliferation in colorectal cancer cell lines. Cancer Lett. 2016; 378(2):104-10. DOI: 10.1016/j.canlet.2016.05.019. View

Fajer M, Meng Y, Roux B . The Activation of c-Src Tyrosine Kinase: Conformational Transition Pathway and Free Energy Landscape. J Phys Chem B. 2016; 121(15):3352-3363. PMC: 5398919. DOI: 10.1021/acs.jpcb.6b08409. View

10.

Boonyaratanakornkit V, Edwards D . Receptor mechanisms mediating non-genomic actions of sex steroids. Semin Reprod Med. 2007; 25(3):139-53. DOI: 10.1055/s-2007-973427. View

11.

Mitra S, Hanson D, Schlaepfer D . Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005; 6(1):56-68. DOI: 10.1038/nrm1549. View

12.

Kopetz S . Targeting SRC and epidermal growth factor receptor in colorectal cancer: rationale and progress into the clinic. Gastrointest Cancer Res. 2009; 1(4 Suppl 2):S37-41. PMC: 2666842. View

13.

Peluso J, Pru J . Progesterone Receptor Membrane Component (PGRMC)1 and PGRMC2 and Their Roles in Ovarian and Endometrial Cancer. Cancers (Basel). 2021; 13(23). PMC: 8656518. DOI: 10.3390/cancers13235953. View

14.

Stahl M, Ferenz C, Kelleher K, Kriz R, Knopf J . Sequence similarity of phospholipase C with the non-catalytic region of src. Nature. 1988; 332(6161):269-72. DOI: 10.1038/332269a0. View

15.

Pina-Medina A, Hansberg-Pastor V, Gonzalez-Arenas A, Cerbon M, Camacho-Arroyo I . Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells. Steroids. 2015; 105:19-25. DOI: 10.1016/j.steroids.2015.11.008. View

16.

Lewis-Tuffin L, Feathers R, Hari P, Durand N, Li Z, Rodriguez F . Src family kinases differentially influence glioma growth and motility. Mol Oncol. 2015; 9(9):1783-98. PMC: 4623998. DOI: 10.1016/j.molonc.2015.06.001. View

17.

Hernandez-Hernandez O, Gonzalez-Garcia T, Camacho-Arroyo I . Progesterone receptor and SRC-1 participate in the regulation of VEGF, EGFR and Cyclin D1 expression in human astrocytoma cell lines. J Steroid Biochem Mol Biol. 2012; 132(1-2):127-34. DOI: 10.1016/j.jsbmb.2012.04.005. View

18.

Jaraiz-Rodriguez M, Tabernero M, Gonzalez-Tablas M, Otero A, Orfao A, Medina J . A Short Region of Connexin43 Reduces Human Glioma Stem Cell Migration, Invasion, and Survival through Src, PTEN, and FAK. Stem Cell Reports. 2017; 9(2):451-463. PMC: 5549880. DOI: 10.1016/j.stemcr.2017.06.007. View

19.

Rothschild S, Gautschi O, Haura E, Johnson F . Src inhibitors in lung cancer: current status and future directions. Clin Lung Cancer. 2010; 11(4):238-42. DOI: 10.3816/CLC.2010.n.030. View

20.

Khalid H, Shibata S, Kishikawa M, Yasunaga A, Iseki M, Hiura T . Immunohistochemical analysis of progesterone receptor and Ki-67 labeling index in astrocytic tumors. Cancer. 1997; 80(11):2133-40. DOI: 10.1002/(sici)1097-0142(19971201)80:11<2133::aid-cncr13>3.0.co;2-#. View