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- Title
The Ca<sup>2+</sup> channel ORAI1 is a regulator of oral cancer growth and nociceptive pain.
- Authors
Son, Ga-Yeon; Tu, Nguyen Huu; Santi, Maria Daniela; Loya Lopez, Santiago; Souza Bomfim, Guilherme H.; Vinu, Manikandan; Zhou, Fang; Chaloemtoem, Ariya; Alhariri, Rama; Idaghdour, Youssef; Khanna, Rajesh; Ye, Yi; Lacruz, Rodrigo S.
- 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. Editor's summary: Oral tumors greatly impair quality of life, in part because of the associated chronic pain that worsens as the disease progresses. Son et al. investigated the role of the Ca2+ channel ORAI1 in oral cancer cells. ORAI1 stimulated the migration of dysplastic oral keratinocytes and the proliferation of oral cancer cells. The enhanced pain sensitivity induced by allograft tumors of oral cancer cells was ablated by ORAI1 deficiency. Oral tumor pain is relayed by trigeminal ganglia, and conditioned medium from oral cancer cells increased the excitability of trigeminal ganglion neurons in an ORAI1-dependent manner. These results suggest that ORAI1 activity could be targeted to reduce oral tumor growth and pain. —Wei Wong
- Subjects
ORAL cancer; NOCICEPTIVE pain; TUMOR growth; CANCER pain; CANCER cell proliferation; MOUTH
- Publication
Science Signaling, 2023, Vol 16, Issue 801, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.adf9535