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STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration

journal contribution
submitted on 2024-01-18, 09:33 and posted on 2024-01-21, 05:10 authored by Ayat S. Hammad, Fang Yu, Jawaher Al-Hamaq, F. David Horgen, Khaled Machaca

Store-operated calcium entry (SOCE) contributes to several physiological and pathological conditions including transcription, secretion, immunodeficiencies, and cancer. SOCE has been shown to be important for breast cancer cell migration where knockdown of SOCE components (STIM1 or Orai1) decreases cancer metastasis. Here we show unexpectedly that complete knockout of STIM1 (STIM1-KO) using gene editing in metastatic MDA-MB-231 breast cancer cells results in faster migration and enhanced invasion capacity. In contrast, Orai1-KO cells, which have similar levels of SOCE inhibition as STIM1-KO, migrate slower than the parental cell line. This shows that the enhanced migration phenotype of STIM1-KO cells is not due to the loss of Ca2+ entry through SOCE, rather it involves transcriptional remodeling as elucidated by RNA-seq analyses. Interestingly, NFAT1 is significantly downregulated in STIM1-KO cells and overexpression of NFAT1 reversed the enhanced migration of STIM1-KO cells. STIM1 knockout in other breast cancer cells, independent of their metastatic potential, also enhanced cell migration while reducing NFAT1 expression. These data argue that in breast cancer cells STIM1 modulates NFAT1 expression and cell migration independently of its role in SOCE.

Other Information

Published in: Cell Calcium
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1016/j.ceca.2023.102779

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Elsevier

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Weill Cornell Medicine - Qatar
  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU