STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration
<p dir="ltr">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 component...
محفوظ في:
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| مؤلفون آخرون: | , , , |
| منشور في: |
2023
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| _version_ | 1864513530396409856 |
|---|---|
| author | Ayat S. Hammad (9592374) |
| author2 | Fang Yu (156838) Jawaher Al-Hamaq (17807807) F. David Horgen (2008633) Khaled Machaca (194372) |
| author2_role | author author author author |
| author_facet | Ayat S. Hammad (9592374) Fang Yu (156838) Jawaher Al-Hamaq (17807807) F. David Horgen (2008633) Khaled Machaca (194372) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ayat S. Hammad (9592374) Fang Yu (156838) Jawaher Al-Hamaq (17807807) F. David Horgen (2008633) Khaled Machaca (194372) |
| dc.date.none.fl_str_mv | 2023-09-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.ceca.2023.102779 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/STIM1_signals_through_NFAT1_independently_of_Orai1_and_SOCE_to_regulate_breast_cancer_cell_migration/25018394 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Oncology and carcinogenesis STIM1 Orai1 Store-operated calcium entry Breast cancer Metastatic NFAT Cell migration Invasion |
| dc.title.none.fl_str_mv | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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 Ca<sup>2+</sup> 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Calcium<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ceca.2023.102779" target="_blank">https://dx.doi.org/10.1016/j.ceca.2023.102779</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_daa907d8de8803acaef3c4403aee7fc9 |
| identifier_str_mv | 10.1016/j.ceca.2023.102779 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25018394 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migrationAyat S. Hammad (9592374)Fang Yu (156838)Jawaher Al-Hamaq (17807807)F. David Horgen (2008633)Khaled Machaca (194372)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesOncology and carcinogenesisSTIM1Orai1Store-operated calcium entryBreast cancerMetastaticNFATCell migrationInvasion<p dir="ltr">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 Ca<sup>2+</sup> 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Calcium<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ceca.2023.102779" target="_blank">https://dx.doi.org/10.1016/j.ceca.2023.102779</a></p>2023-09-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.ceca.2023.102779https://figshare.com/articles/journal_contribution/STIM1_signals_through_NFAT1_independently_of_Orai1_and_SOCE_to_regulate_breast_cancer_cell_migration/25018394CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/250183942023-09-01T00:00:00Z |
| spellingShingle | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration Ayat S. Hammad (9592374) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Oncology and carcinogenesis STIM1 Orai1 Store-operated calcium entry Breast cancer Metastatic NFAT Cell migration Invasion |
| status_str | publishedVersion |
| title | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration |
| title_full | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration |
| title_fullStr | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration |
| title_full_unstemmed | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration |
| title_short | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration |
| title_sort | STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Oncology and carcinogenesis STIM1 Orai1 Store-operated calcium entry Breast cancer Metastatic NFAT Cell migration Invasion |