Abstract
The acidic vesicles of the endolysosomal (EL) system are emerging as an intracellular Ca2+ store implicated in the regulation of multiple cellular functions. The EL Ca2+ store releases Ca2+ through a variety of Ca2+-permeable channels, including Transient Receptor Potential (TRP) Mucolipin 1-3 (TRPML1-3) and two-pore channels 1-2 (TPC1-2), whereas EL Ca2+ refilling is sustained by the proton gradient across the EL membrane and/or by the endoplasmic reticulum (ER). EL Ca2+ signals may be either spatially restricted to control vesicle trafficking, autophagy and membrane repair or may be amplified into a global Ca2+ signal through the Ca2+-dependent recruitment of ER-embedded channels. Emerging evidence suggested that nicotinic acid adenine dinucleotide phosphate (NAADP)-gated TPCs sustain multiple cancer hallmarks, such as migration, invasiveness and angiogenesis. Herein, we first survey the EL Ca2+ refilling and release mechanisms and then focus on the oncogenic role of EL Ca2+ signaling. While the evidence in favor of TRPML1 involvement in neoplastic transformation is yet to be clearly provided, TPCs are emerging as an alternative target for anticancer therapies.
| Original language | English |
|---|---|
| Article number | 27 |
| Journal | Cancers |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- Angiogenesis
- Cancer
- Endolysosomal Ca signaling
- Metastasis
- NAADP
- Proliferation
- TPCs
- TRPML1
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Endolysosomal Ca 2+ signalling and cancer hallmarks : Two-pore channels on the move, TRPML1 lags behind! / Faris, Pawan; Shekha, Mudhir; Montagna, Daniela; Guerra, Germano; Moccia, Francesco.
In: Cancers, Vol. 11, No. 1, 27, 01.01.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Endolysosomal Ca 2+ signalling and cancer hallmarks
T2 - Two-pore channels on the move, TRPML1 lags behind!
AU - Faris, Pawan
AU - Shekha, Mudhir
AU - Montagna, Daniela
AU - Guerra, Germano
AU - Moccia, Francesco
PY - 2019/1/1
Y1 - 2019/1/1
N2 - The acidic vesicles of the endolysosomal (EL) system are emerging as an intracellular Ca2+ store implicated in the regulation of multiple cellular functions. The EL Ca2+ store releases Ca2+ through a variety of Ca2+-permeable channels, including Transient Receptor Potential (TRP) Mucolipin 1-3 (TRPML1-3) and two-pore channels 1-2 (TPC1-2), whereas EL Ca2+ refilling is sustained by the proton gradient across the EL membrane and/or by the endoplasmic reticulum (ER). EL Ca2+ signals may be either spatially restricted to control vesicle trafficking, autophagy and membrane repair or may be amplified into a global Ca2+ signal through the Ca2+-dependent recruitment of ER-embedded channels. Emerging evidence suggested that nicotinic acid adenine dinucleotide phosphate (NAADP)-gated TPCs sustain multiple cancer hallmarks, such as migration, invasiveness and angiogenesis. Herein, we first survey the EL Ca2+ refilling and release mechanisms and then focus on the oncogenic role of EL Ca2+ signaling. While the evidence in favor of TRPML1 involvement in neoplastic transformation is yet to be clearly provided, TPCs are emerging as an alternative target for anticancer therapies.
AB - The acidic vesicles of the endolysosomal (EL) system are emerging as an intracellular Ca2+ store implicated in the regulation of multiple cellular functions. The EL Ca2+ store releases Ca2+ through a variety of Ca2+-permeable channels, including Transient Receptor Potential (TRP) Mucolipin 1-3 (TRPML1-3) and two-pore channels 1-2 (TPC1-2), whereas EL Ca2+ refilling is sustained by the proton gradient across the EL membrane and/or by the endoplasmic reticulum (ER). EL Ca2+ signals may be either spatially restricted to control vesicle trafficking, autophagy and membrane repair or may be amplified into a global Ca2+ signal through the Ca2+-dependent recruitment of ER-embedded channels. Emerging evidence suggested that nicotinic acid adenine dinucleotide phosphate (NAADP)-gated TPCs sustain multiple cancer hallmarks, such as migration, invasiveness and angiogenesis. Herein, we first survey the EL Ca2+ refilling and release mechanisms and then focus on the oncogenic role of EL Ca2+ signaling. While the evidence in favor of TRPML1 involvement in neoplastic transformation is yet to be clearly provided, TPCs are emerging as an alternative target for anticancer therapies.
KW - Angiogenesis
KW - Cancer
KW - Endolysosomal Ca signaling
KW - Metastasis
KW - NAADP
KW - Proliferation
KW - TPCs
KW - TRPML1
UR - http://www.scopus.com/inward/record.url?scp=85061892961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061892961&partnerID=8YFLogxK
U2 - 10.3390/cancers11010027
DO - 10.3390/cancers11010027
M3 - Review article
AN - SCOPUS:85061892961
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 1
M1 - 27
ER -