Nuclear transport proteins are secreted by cancer cells and identified as potential novel cancer biomarkers

Abstract

Previous studies have identified increased expression of members of the nuclear transport protein family in cancer cells. Recently, certain nuclear transport proteins have been reported to be secreted by cells and found in the serum. The aims of our study were to investigate the levels of multiple nuclear transport proteins secreted from cancer cells, and to determine their potential as diagnostic markers for cervical and oesophageal cancer. Mass spectrometry identified 10 nuclear transport proteins in the secretome and exosomes of cultured cancer cells, and Western blot analysis confirmed increased secreted levels in cancer cells compared to normal. To investigate their presence in patient serum, enzyme‐linked immunosorbent assays were performed and revealed significantly increased levels of KPNβ1, CRM1, CAS, IPO5 and TNPO1 in cervical and oesophageal cancer patient serum compared to non‐cancer controls. Significantly elevated KPNα2 and RAN levels were also identified in oesophageal cancer serum samples. Logistics regression analyses revealed IPO5 and TNPO1 to be the best performing individual candidate biomarkers in discriminating between cancer cases and controls. The combination of KPNβ1, CRM1, KPNα2, CAS, RAN, IPO5 and TNPO1 as a panel of biomarkers had the highest diagnostic capacity with an area under the curve of 0.944 and 0.963, for cervical cancer and oesophageal cancer, and sensitivity of 92.5% at 86.8% specificity and 95.3% sensitivity at 87.5% specificity, respectively. These results suggest that nuclear transport proteins have potential as diagnostic biomarkers for cervical and oesophageal cancers, with a combination of protein family members being the best predictor.

Heavy Ion-Responsive lncRNA EBLN3P Functions in the Radiosensitization of Non-Small Cell Lung Cancer Cells Mediated by TNPO1

“…In other words, the miR-144-3p antagonist could rescue the knockdown effects of LNC EBLN3P, thereby allowing normal cell proliferation, which is indicative of their direct regulatory relationship. In addition, TNPO1 is identified as an oncogene and has been reported to be associated with the development of esophageal cancer and cervical cancer [9,26], consistent with our finding that TNPO1-knockdown inhibited proliferation of A549 cells. In our study, we reveal that the knockdown of LNC EBLN3P induced by carbon ion irradiation could inhibit cell proliferation and induce apoptosis and radiosensitivity of NSCLC cells through the down-regulation of TNPO1, demonstrating that TNPO1 may be a key factor functioning in the radiobiological effects of heavy ions.…”

Activin and BMP Signalling in Human Testicular Cancer Cell Lines, and a Role for the Nucleocytoplasmic Transport Protein Importin-5 in Their Crosstalk

“…IPO5 is elevated in colorectal cancers and oesophageal cancer, and this has been associated with increased tumorigenicity and metastasis [ 98 , 99 ]. Elevated IPO5 levels in the serum of oesophageal and cervical cancer patients has been proposed as a cancer biomarker [ 100 ]. We had previously demonstrated that IPO5 transcript and protein are abundant in foetal germ cells [ 40 , 42 ], GCNIS, seminomas, and in TCam-2 cells [ 45 ].…”

Quantitative Proteomics for the Identification of Differentially Expressed Proteins in the Extracellular Vesicles of Cervical Cancer Cells

“…However, the observed results from the EVs of cervical cancer and other different malignancies propose them as potential therapeutic or diagnostic targets for this cancer. Initially, their utility as biomarkers was suggested due to the detection of their protein content (KPNB1, CRM1, CAS, IPO5, and TNPO1) in the serum of patients with cervical cancer [ 69 ]. However, the evaluation of any EV molecule as a possible marker or therapeutic target will be random if it is unknown whether it is found to be modified in the EVs in this cancer.…”