Vol. 123, No. 1 (Supplement) 2018
Supplement abstract

Stim and Orai mediate constitutive Ca2+ entry and control endoplasmic reticulum Ca2+ refilling in primary cultures of colorectal carcinoma cells

Germano Guerra
Università degli Studi del Molise, Dipartimento di Medicina e Scienze della Salute “Vincenzo Tiberio”, Campobasso, Italia
Estella Zuccolo
Università degli Studi di Pavia, Dipartimento di Biologia Biotecnologie “Lazzaro Spallanzani”, Pavia, Italia
Umberto Laforenza
Università degli studi di Pavia, Dipartimento di Medicina Molecolare, Pavia, Italia
Pawan Farisa
Università di Salahaddin, Erbil, Kurdistan-Region of Iraq, Iraq, Dipartimento di Biologia, College of Science, Erbil, Iraq
Angela Lucariello
Università degli Studi del Molise, Dipartimento di Medicina e Scienze della Salute “Vincenzo Tiberio”, Campobasso, Italia
Angelica Perna
Università degli Studi del Molise, Dipartimento di Medicina e Scienze della Salute “Vincenzo Tiberio”, Campobasso, Italia
Antonio De Luca
Università degli Studi della Campania “Luigi Vanvitelli”, Dipartimento di Salute Fisica e Mentale e Medicina Preventiva, Caserta, Italia
Domenico Tafuri
Università degli Studi di Napoli “Parthenope”, Dipartimento di Scienze Motorie e del Benessere, Napoli, Italia
Marcello Maestri
Fondazione IRCCS Policlinico San Matteo, Unità Operativa Complessa di Chirurgia Generale, Pavia, Italia
Dlzar Ali Kheder
Università di Zakho, Zakho, Kurdistan-Region of Iraq, Dipartimento di Biologia, Zakho, Iraq
Paolo Pedrazzoli
Università degli Studi di Pavia, Dipartimento of Scienze Clinico Chirurgiche, Diagnostiche e Pediatriche, Pavia, Italia
Daniela Montagna
Fondazione IRCCS Policlinico San Matteo, Laboratorio di Immunologia e Trapiantologia, Pavia, Italia
Francesco Moccia
Università degli Studi di Pavia, Dipartimento di Biologia Biotecnologie “Lazzaro Spallanzani”, Pavia, Italia

Published 2018-12-30

Keywords

  • Colorectal cancer,
  • store-operated Ca2 entry,
  • Stim,
  • Orai,
  • proliferation

How to Cite

Guerra, G., Zuccolo, E., Laforenza, U., Farisa, P., Lucariello, A., Perna, A., De Luca, A., Tafuri, D., Maestri, M., Kheder, D. A., Pedrazzoli, P., Montagna, D., & Moccia, F. (2018). Stim and Orai mediate constitutive Ca2+ entry and control endoplasmic reticulum Ca2+ refilling in primary cultures of colorectal carcinoma cells. Italian Journal of Anatomy and Embryology, 123(1), 114. https://doi.org/10.13128/ijae-11420

Abstract

Store-operated Ca2+ entry (SOCE) provides a major Ca2+ entry route in cancer cells. SOCE is mediated by the assembly of Stim and Orai proteins at endoplasmic reticulum (ER)-plasma mem- brane junctions upon depletion of the ER Ca2+ store. Additionally, Stim and Orai proteins underpin constitutive Ca2+ entry in a growing number of cancer cell types due to the partial depletion of their ER Ca2+ reservoir. Herein, we investigated for the first time the structure and function of SOCE in primary cultures of colorectal carcinoma (CRC) established from primary tumor (pCRC) and meta- static lesions (mCRC) of human subjects. Stim1-2 and Orai1-3 transcripts were equally expressed in pCRC and mCRC cells, although Stim1 and Orai3 proteins were up-regulated in mCRC cells. TheMn2+-quenching technique revealed that constitutive Ca2+ entry was significantly enhanced in pCRC cells and was inhibited by the pharmacological and genetic blockade of Stim1, Stim2, Orai1 and Orai3. The larger resting Ca2+ influx in pCRC was associated to their lower ER Ca2+ content as compared to mCRC cells. Pharmacological and genetic blockade of Stim1, Stim2, Orai1 and Orai3 prevented ER-dependent Ca2+ release, thereby suggesting that constitutive SOCE maintains ER Ca2+ levels. Nevertheless, pharmacological and genetic blockade of Stim1, Stim2, Orai1 and Orai3 did not affect CRC cell proliferation and migration. These data provide the first evidence that Stim and Orai proteins mediate constitutive Ca2+ entry and replenish ER with Ca2+ in primary cultures of CRC cells. However, SOCE is not a promising target to design for alternative therapies for CRC.

References

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