Nirmal Kumar Ramasamy and Nithya Thangam and Saravanan and Vinitha Devaraj and Sankaravel and Rajan Thinakaran and Shalini Ganeshan (2025) ORAI1 Gene and Calcium Deficiency in Oral Cancer: An Overview. ORAI1 Gene and Calcium Deficiency in Oral Cancer: An Overview, 41 (2). pp. 1-4. ISSN 0970-020 X

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Abstract

Oral cancer, which includes malignancies of the lip, tongue, and mouth, ranks as the
sixth most prevalent cancer globally, with approximately 355,000 new cases and 177,000 deaths
annually. Over the past 25 years, its incidence has risen significantly among young individuals and
women, while the decline in mortality rates remains minimal. Among these cases, oral squamous
cell carcinomas (OSCCs) account for nearly 90%, originating primarily from squamous cells in
the oral cavity and lips. Nutritional deficiencies, particularly inadequate levels of vitamins D, C,
B, and A, along with protein-energy malnutrition (PEM), have been associated with various oral
health issues, including enamel hypoplasia and periodontal disease. A lack of calcium, in particular,
weakens alveolar bone density and compromises oral mucosal resistance, making tissues more
vulnerable to carcinogenic agents. Recent studies suggest a link between calcium deficiency and
the overexpression of the ORAI1 gene, which regulates store-operated calcium entry (SOCE) and
plays a crucial role in tumorigenesis. Elevated ORAI1 expression in OSCC has been linked to
prolonged calcium influx, disruptions in ion homeostasis, and increased cancer cell proliferation,
migration, and pain modulation. The oncogenic activation of ORAI1 and its associated calcium
channels (Orai-2 and Orai-3) interferes with key signalling pathways such as Akt, NF-κB, and
mTOR, thereby promoting tumour progression. Furthermore, tobacco-derived carcinogens like
4-NQO and NNN have been shown to upregulate ORAI1 and Orai-2 expression in oral cancer
cell lines. A deeper understanding of the connection between calcium deficiency and ORAI1
overexpression in OSCC may offer valuable insights for developing targeted therapies aimed at
regulating abnormal calcium signalling in oral cancer cells.

Item Type: Article
Uncontrolled Keywords: Oral cancer, Oral squamous cell carcinoma, Calcium deficiency, ORAI1, Store-operated calcium entry
Divisions: PSG College of Arts and Science > Department of Microbiology
PSG College of Arts and Science > Department of Botany
PSG College of Arts and Science > Department of Biochemistry
Depositing User: Dr. B Sivakumar
Date Deposited: 27 Mar 2026 08:31
Last Modified: 27 Mar 2026 08:31
URI: https://ir.psgcas.ac.in/id/eprint/2752

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