Biomarker: KPNA2

Histology type: endometrial carcinoma

Stage: aggressive

Country: Switzerland

Region: Zurich

Followed up time :

Subgroup 1 name : <10%

Subgroup 1 number: 371

Subgroup 2 name: ≥10%

Subgroup 2 number: 105

Conclusion: KPNA2 is overexpressed in human and mouse endometrial cancers and promotes cellular proliferation. Introducing KPNA2 immunohistochemistry in routine diagnostics may allow for the identification of patients who need more aggressive treatment regimens.

Sample type : tissue

Sample method: immunohistochemistry 

Expression pattern : nuclear overexpression

Expression elevation: For the analysis of KPNA2 staining, the percentage of tumour cells with nuclear immunoreactivity was quantified. Based on initial breast cancer studies , KPNA2 positivity was defined as strong nuclear staining in at least 10% of nuclei

Statictics: cutoff<68;cutoff>68

Cohort age: 250;226

Subgroup 1 age: 199;172

Subgroup 2 age: 51;54

Funtion description: KPNA2 expression was significantly up-regulated in human endometrial carcinomas, activation of the PI3K/AKT pathway, and epithelial-mesenchymal transition. In the mouse model, KPNA2 showed increased expression levels from precancerous (EmgD, EIC) to far-advanced invasive lesions. Investigated the cell proliferation capacity after siRNA-mediated KPNA2 knockdown in the human endometrial cancer cell line MFE-296. KPNA2 silencing led to decreased proliferation of the cancer cells, suggesting interplay of the protein with the cell cycle. The mechanism of enhanced nucleocytoplasmic transport by KPNA2 overexpression seems a common event in aggressive cancers since we have shown a significant correlation of KPNA2 expression and tumour aggressiveness in a large variety of other solid tumour entities.

Funtion Uniprot: Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.

UniProt ID: P52292

UniProt Link: https://www.uniprot.org/uniprotkb/P52292/entry

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed ubiquitously.

Subcellular UniProt: #Cytoplasm #Endoplasmic reticulum #Golgi apparatus #Membrane #Nucleus

Alternative name from UniProt:

Recommended name: Importin subunit alpha-1

Gene name from HGNC: KPNA2 (IPOA1, QIP2, RCH1, SRP1alpha)

HPA class: Plasma proteins Transporters

AlphaFold DB: P52292

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P52292

HPA link: https://www.proteinatlas.org/ENSG00000182481-KPNA2

Tissue specificity RNA from HPA: Tissue enhanced (testis)

Tissue expression from HPA: Nuclear expression in subsets of cells in most tissues.

Single cell type specificity Cell type enhanced (Early spermatids, Spermatocytes, Extravillous trophoblasts)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm, Cytosol (Single cell variability, CCD Protein, CCD Transcript)

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), liver cancer (unfavorable), urothelial cancer (unfavorable), colorectal cancer (favorable) and lung cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000182481-KPNA2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000182481-KPNA2/pathology/endometrial+cancer

OMIM: 600685

OMIM link2: https://www.omim.org/entry/600685

HGNC ID: HGNC:6395

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6395