Protective role of IRBIT on sodium bicarbonate cotransporter-n1 for migratory cancer cells

Soyoung Hwang, Dong Min Shin, Jeong Hee Hong

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

IP3 receptor-binding protein released with IP3 (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to cancer metastasis. The effect of IRBIT on NBCn1 and its relation to cancer cell migration remain obscure. We therefore aimed to determine the effect of IRBIT on NBCn1 and the regulation of cancer cell migration due to IRBIT-induced alterations in NBCn1 activity. Overexpression of IRBIT enhanced cancer cell migration and NBC activity. Knockdown of IRBIT or NBCn1 and treatment with an NBC-specific inhibitor, S0859, attenuated cell migration. Stimulation with oncogenic epidermal growth factor enhanced the expression of NBCn1 and migration of cancer cells by recruiting IRBIT. The recruited IRBIT stably maintained the expression of the NBCn1 transporter machinery in the plasma membrane. Combined inhibition of IRBIT and NBCn1 dramatically inhibited the migration of cancer cells. Combined modulation of IRBIT and NBCn1 offers an effective strategy for attenuating cancer metastasis.

Original languageEnglish
Article number816
Pages (from-to)1-19
Number of pages19
JournalPharmaceutics
Volume12
Issue number9
DOIs
Publication statusPublished - 2020 Sep

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT; [2019R1F1A1046785, JHH] and [2020R1A2C2003409, DMS]). All plasmid constructs were kindly provided by Shmuel Muallem (National Institutes of Health, National Institute of Dental and Craniofacial Research, Bethesda, MD).

Funding Information:
Funding: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT; [2019R1F1A1046785, JHH] and [2020R1A2C2003409, DMS]).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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