High Expression of Orai1 Enhances Cell Proliferation and is Associated with Poor Prognosis in Human Colorectal Cancer.
BACKGROUND
Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ influx mechanism in non-excitable cells and regulates a variety of cellular functions. As the essential channel pore-forming protein of SOCE, Orai1 has recently been implicated in carcinogenesis and tumor progression in multiple malignancies. However, the role of Orai1 in colorectal cancer (CRC) has not been investigated.


METHODS
The expression of Orai1 in 21 CRC specimens was examined by immunohistochemistry (IHC) staining, Western blot, and qRT-PCR. The results were compared with paired non-tumor tissues. The expression of Orai1 in additional specimens of 129 CRC patients was examined by IHC staining and the IHC scores were compared with clinicopathological features. After knock-down of the expression of Orai1 in LoVo cells, cell proliferation was examined using a MTT assay and colony formation assay. Flow cytometry was also used to detect apoptosis.


RESULTS
The expression of Orai1 was upregulated in human CRC tissues, high expression of Orai1 was closely associated with depth of tumor invasion, lymph node metastasis, and perineural invasion, and patients with high expression of Orai1 had shorter overall survival. Moreover, the expression of Orai1 was also upregulated in CRC cell lines, knockdown of Orai1 inhibited cell proliferation, the effect of growth inhibition was not due to enhanced apoptosis, and stromal interaction molecule1 (STIM1) did not take part in the regulation of CRC cell proliferation.


CONCLUSIONS
Orai1 is crucial to sustained CRC cell proliferation, high expression of Orai1 is associated with tumor progression and poor prognosis, and Orai1 may be a promising target for prognosis and treatment of CRC.
Lin
L
Gui
Zhenjun
Z
Wang
Jiagang
J
Han
Huachong
H
Ma
Zhulin
Z
Li
D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein / Q000378:metabolism*; D011379:Prognosis; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000071737:Stromal Interaction Molecule 1 / Q000378:metabolism; D015854:Up-Regulation
D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium