Cancers, Vol. 11, Pages 542: Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Induces Intracellular Ca2+ Release through the Two-Pore Channel TPC1 in Metastatic Colorectal Cancer Cells
Cancers, Vol. 11, Pages 542: Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Induces Intracellular Ca2+ Release through the Two-Pore Channel TPC1 in Metastatic Colorectal Cancer Cells
Cancers doi: 10.3390/cancers11040542
Authors:
Pawan Faris
Giorgia Pellavio
Federica Ferulli
Francesca Di Nezza
Mudhir Shekha
Dmitry Lim
Marcello Maestri
Germano Guerra
Luigi Ambrosone
Paolo Pedrazzoli
Umberto Laforenza
Daniela Montagna
Francesco Moccia
Nicotinic acid adenine dinucleotide phosphate (NAADP) gates two-pore channels 1 and 2 (TPC1 and TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced EL Ca2+ signals may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced Ca2+ release mechanism (CICR). Herein, we aimed at assessing for the first time the role of EL Ca2+ signaling in primary cultures of human metastatic colorectal carcinoma (mCRC) by exploiting Ca2+ imaging and molecular biology techniques. The lysosomotropic agent, Gly-Phe β-naphthylamide (GPN), and nigericin, which dissipates the ΔpH which drives Ca2+ refilling of acidic organelles, caused massive Ca2+ release in the presence of a functional inositol-1,4,5-trisphosphate (InsP3)-sensitive ER Ca2+ store. Liposomal delivery of NAADP induced a transient Ca2+ release that was reduced by GPN and NED-19, a selective TPC antagonist. Pharmacological and genetic manipulations revealed that the Ca2+ response to NAADP was triggered by TPC1, the mos...
Source: Cancers - Category: Cancer & Oncology Authors: Pawan Faris Giorgia Pellavio Federica Ferulli Francesca Di Nezza Mudhir Shekha Dmitry Lim Marcello Maestri Germano Guerra Luigi Ambrosone Paolo Pedrazzoli Umberto Laforenza Daniela Montagna Francesco Moccia Tags: Article Source Type: research
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