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Orai-1 and Orai-2 regulate oral cancer cell migration and colonisation by suppressing Akt/mTOR/NF-κB signalling

Anuj Kumar Singh1, Nand Kishor Roy1, Devivasha Bordoloi1

  • 1Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.

Life Sciences
|September 4, 2020
PubMed

Insights

Oral cancer cells overexpress Orai-1 and Orai-2 proteins, which regulate calcium entry. Inhibiting these proteins suppresses oral cancer growth and migration, suggesting they are potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Calcium Signaling

Background:

  • Oral cancer (OC) remains a significant global health challenge despite treatment advances.
  • Dysregulated calcium signaling is implicated in various cancers.
  • Store-operated calcium entry (SOCE) is a key calcium influx mechanism regulated by Orai and STIM proteins.

Purpose of the Study:

  • To investigate the role of Orai-1 and Orai-2 in oral cancer.
  • To elucidate the underlying molecular mechanisms involving Orai-1 and Orai-2 in oral cancer progression.

Main Methods:

  • Quantitative analysis of Orai-1 and Orai-2 expression in oral cancer tissues and cell lines.
  • Inhibition of Orai-1 and Orai-2 using chemical inhibitors and siRNAs.
  • Assessment of cellular proliferation, colony formation, and migration.
  • Analysis of the Akt/mTOR/NF-κB signaling pathway.
  • Evaluation of Orai-1 and Orai-2 expression following exposure to carcinogens (NNN and 4-NQO).

Main Results:

  • Orai-1 and Orai-2 proteins were significantly overexpressed in oral cancer tissues and cell lines compared to normal controls.
  • Silencing Orai-1 and Orai-2 reduced calcium uptake and inhibited oral cancer cell proliferation, colony formation, and migration.
  • Orai-1 and Orai-2 silencing led to the inhibition of the Akt/mTOR/NF-κB pathway.
  • Exposure to tobacco carcinogen NNN and synthetic carcinogen 4-NQO increased Orai-1 and Orai-2 expression in oral cancer cells.

Conclusions:

  • Orai-1 and Orai-2 play a crucial role in oral cancer development and progression.
  • Targeting Orai-1 and Orai-2 presents a promising therapeutic strategy for oral cancer.
  • Carcinogen exposure can upregulate Orai-1 and Orai-2, potentially contributing to oral carcinogenesis.
Keywords:
CalciumOraiOral cancerSOCESTIM

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