The Ca2+ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain

Ga Yeon Son; Nguyen Huu Tu; Maria Daniela Santi; Santiago Loya Lopez; Guilherme H. Souza Bomfim; Manikandan Vinu; Fang Zhou; Ariya Chaloemtoem; Rama Alhariri; Youssef Idaghdour; Rajesh Khanna; Yi Ye; Rodrigo S. Lacruz

doi:10.1126/scisignal.adf9535

The Ca²⁺ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain

Ga Yeon Son, Nguyen Huu Tu, Maria Daniela Santi, Santiago Loya Lopez, Guilherme H. Souza Bomfim, Manikandan Vinu, Fang Zhou, Ariya Chaloemtoem, Rama Alhariri, Youssef Idaghdour, Rajesh Khanna, Yi Ye, Rodrigo S. Lacruz

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca²⁺ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca²⁺ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.

Original language	English (US)
Article number	eadf9535
Journal	Science signaling
Volume	16
Issue number	801
DOIs	https://doi.org/10.1126/scisignal.adf9535
State	Published - 2023
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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title = "The Ca2+ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain",

abstract = "Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca2+ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca2+ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.",

author = "Son, {Ga Yeon} and Tu, {Nguyen Huu} and Santi, {Maria Daniela} and Lopez, {Santiago Loya} and {Souza Bomfim}, {Guilherme H.} and Manikandan Vinu and Fang Zhou and Ariya Chaloemtoem and Rama Alhariri and Youssef Idaghdour and Rajesh Khanna and Yi Ye and Lacruz, {Rodrigo S.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors, some rights reserved.",

year = "2023",

doi = "10.1126/scisignal.adf9535",

language = "English (US)",

volume = "16",

journal = "Science signaling",

issn = "1945-0877",

publisher = "American Association for the Advancement of Science",

number = "801",

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T1 - The Ca2+ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain

AU - Son, Ga Yeon

AU - Tu, Nguyen Huu

AU - Santi, Maria Daniela

AU - Lopez, Santiago Loya

AU - Souza Bomfim, Guilherme H.

AU - Vinu, Manikandan

AU - Zhou, Fang

AU - Chaloemtoem, Ariya

AU - Alhariri, Rama

AU - Idaghdour, Youssef

AU - Khanna, Rajesh

AU - Ye, Yi

AU - Lacruz, Rodrigo S.

PY - 2023

Y1 - 2023

N2 - Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca2+ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca2+ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.

AB - Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca2+ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca2+ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.

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The Ca²⁺ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain

Abstract

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