TRP Channels and STIM/ORAI Proteins: Sensors and Effectors of Cancer and Stroma Cell Migration

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2014 Apr 15

PMID 24724725

Citations 36

Authors

N Nielsen

O Lindemann

A Schwab

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Cancer cells are strongly influenced by host cells within the tumour stroma and vice versa. This leads to the development of a tumour microenvironment with distinct physical and chemical properties that are permissive for tumour progression. The ability to migrate plays a central role in this mutual interaction. Migration of cancer cells is considered as a prerequisite for tumour metastasis and the migration of host stromal cells is required for reaching the tumour site. Increasing evidence suggests that transient receptor potential (TRP) channels and STIM/ORAI proteins affect key calcium-dependent mechanisms implicated in both cancer and stroma cell migration. These include, among others, cytoskeletal remodelling, growth factor/cytokine signalling and production, and adaptation to tumour microenvironmental properties such as hypoxia and oxidative stress. In this review, we will summarize the current knowledge regarding TRP channels and STIM/ORAI proteins in cancer and stroma cell migration. We focus on how TRP channel or STIM/ORAI-mediated Ca(2+) signalling directly or indirectly influences cancer and stroma cell migration by affecting the above listed mechanisms.

Linked Articles: This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.

Citing Articles

Mechanism of Ca overload caused by STIM1/ORAI1 activation of store-operated Ca entry (SOCE) in hydrogen peroxide-induced mitochondrial damage and apoptosis in human primary melanocytes.

Li Z, Yu Y, Cao X, Wang Y, Lu J, Feng Y Mol Biol Rep. 2025; 52(1):223.

PMID: 39937331 DOI: 10.1007/s11033-025-10329-1.

Delivery of siRNAs Against Selective Ion Channels and Transporter Genes Using Hyaluronic Acid-coupled Carbonate Apatite Nanoparticles Synergistically Inhibits Growth and Survival of Breast Cancer Cells.

Uddin M, Banaszak Holl M, Chowdhury E Int J Nanomedicine. 2024; 19:7709-7727.

PMID: 39099788 PMC: 11297548. DOI: 10.2147/IJN.S440419.

ORAI Ca Channels in Cancers and Therapeutic Interventions.

Zhang Q, Wang C, He L Biomolecules. 2024; 14(4).

PMID: 38672434 PMC: 11048467. DOI: 10.3390/biom14040417.

Pregnancy-Specific Beta-1-Glycoprotein 1 Increases HTR-8/SVneo Cell Migration through the Orai1/Akt Signaling Pathway.

Wang Q, Fang Y, Li Y, Liu H, Zhu M, Hu X Biomolecules. 2024; 14(3).

PMID: 38540713 PMC: 10968057. DOI: 10.3390/biom14030293.

Peritoneal high-fat environment promotes peritoneal metastasis of gastric cancer cells through activation of NSUN2-mediated ORAI2 m5C modification.

Liu K, Xu P, Lv J, Ge H, Yan Z, Huang S Oncogene. 2023; 42(24):1980-1993.

PMID: 37130916 DOI: 10.1038/s41388-023-02707-5.

References

Fiorio Pla A, Ong H, Cheng K, Brossa A, Bussolati B, Lockwich T . TRPV4 mediates tumor-derived endothelial cell migration via arachidonic acid-activated actin remodeling. Oncogene. 2011; 31(2):200-12. PMC: 5934994. DOI: 10.1038/onc.2011.231. View

Prevarskaya N, Ouadid-Ahidouch H, Skryma R, Shuba Y . Remodelling of Ca2+ transport in cancer: how it contributes to cancer hallmarks?. Philos Trans R Soc Lond B Biol Sci. 2014; 369(1638):20130097. PMC: 3917351. DOI: 10.1098/rstb.2013.0097. View

Wells A, Huttenlocher A, Lauffenburger D . Calpain proteases in cell adhesion and motility. Int Rev Cytol. 2005; 245:1-16. DOI: 10.1016/S0074-7696(05)45001-9. View

Gwack Y, Srikanth S, Oh-Hora M, Hogan P, Lamperti E, Yamashita M . Hair loss and defective T- and B-cell function in mice lacking ORAI1. Mol Cell Biol. 2008; 28(17):5209-22. PMC: 2519726. DOI: 10.1128/MCB.00360-08. View

Koukourakis M, Giatromanolaki A, Harris A, Sivridis E . Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res. 2006; 66(2):632-7. DOI: 10.1158/0008-5472.CAN-05-3260. View

Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M . Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007; 109(9):3812-9. DOI: 10.1182/blood-2006-07-035972. View

Waris G, Ahsan H . Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog. 2006; 5:14. PMC: 1479806. DOI: 10.1186/1477-3163-5-14. View

Meng X, Cai C, Wu J, Cai S, Ye C, Chen H . TRPM7 mediates breast cancer cell migration and invasion through the MAPK pathway. Cancer Lett. 2013; 333(1):96-102. DOI: 10.1016/j.canlet.2013.01.031. View

Nabi I . The polarization of the motile cell. J Cell Sci. 1999; 112 ( Pt 12):1803-11. DOI: 10.1242/jcs.112.12.1803. View

10.

Webb B, Chimenti M, Jacobson M, Barber D . Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011; 11(9):671-7. DOI: 10.1038/nrc3110. View

11.

Vaisitti T, Audrito V, Serra S, Bologna C, Brusa D, Malavasi F . NAD+-metabolizing ecto-enzymes shape tumor-host interactions: the chronic lymphocytic leukemia model. FEBS Lett. 2011; 585(11):1514-20. DOI: 10.1016/j.febslet.2011.04.036. View

12.

Schneider S, Pagel P, Rotsch C, Danker T, Oberleithner H, Radmacher M . Volume dynamics in migrating epithelial cells measured with atomic force microscopy. Pflugers Arch. 2000; 439(3):297-303. DOI: 10.1007/s004249900176. View

13.

Yang S, Zhang J, Huang X . Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell. 2009; 15(2):124-34. DOI: 10.1016/j.ccr.2008.12.019. View

14.

Zhao Y, Malinin N, Meller J, Ma Y, West X, Bledzka K . Regulation of cell adhesion and migration by Kindlin-3 cleavage by calpain. J Biol Chem. 2012; 287(47):40012-20. PMC: 3501071. DOI: 10.1074/jbc.M112.380469. View

15.

Li J, Zhang S, Soto X, Woolner S, Amaya E . ERK and phosphoinositide 3-kinase temporally coordinate different modes of actin-based motility during embryonic wound healing. J Cell Sci. 2013; 126(Pt 21):5005-17. PMC: 3820245. DOI: 10.1242/jcs.133421. View

16.

Wei C, Wang X, Chen M, Ouyang K, Song L, Cheng H . Calcium flickers steer cell migration. Nature. 2009; 457(7231):901-5. PMC: 3505761. DOI: 10.1038/nature07577. View

17.

Sours-Brothers S, Ding M, Graham S, Ma R . Interaction between TRPC1/TRPC4 assembly and STIM1 contributes to store-operated Ca2+ entry in mesangial cells. Exp Biol Med (Maywood). 2009; 234(6):673-82. DOI: 10.3181/0809-RM-279. View

18.

Schwab A, Gabriel K, Finsterwalder F, Folprecht G, Greger R, Kramer A . Polarized ion transport during migration of transformed Madin-Darby canine kidney cells. Pflugers Arch. 1995; 430(5):802-7. DOI: 10.1007/BF00386179. View

19.

Dixit N, Yamayoshi I, Nazarian A, Simon S . Migrational guidance of neutrophils is mechanotransduced via high-affinity LFA-1 and calcium flux. J Immunol. 2011; 187(1):472-81. PMC: 3414252. DOI: 10.4049/jimmunol.1004197. View

20.

Yang Z, Wang X, Wang H, Hu L . Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells. Asian J Androl. 2009; 11(2):157-65. PMC: 3735032. DOI: 10.1038/aja.2009.1. View