Table 1.
Protein localization in normal cells and in cancer cells
| Protein | Subcellular localization | Mislocalization mechanisms in cancer | Function of protein mislocalization | Reference | |
|---|---|---|---|---|---|
| Normal cells | Cancer cells | ||||
| Breast Cancer Gene 1 (BRCA1) | Nucleus | Cytoplasm | Mutations on exon 11 result in splicing variants lacking NLS; p53 may promote BRCA1 nuclear export by interrupting the association of BRCA1 with BARD 1 | Nuclear BRCA1 functions in DNA repair and cell-cycle checkpoints, whereas cytoplasmic BRCA1 regulates centrosome function and p53-independent apoptosis | [137–142] |
| p53 | Nucleus | Nucleus Mitochondria, Cytoplasm | Mutations; interaction with MDM2; CRM1-mediated nuclear export | Loss of tumor suppressor function; p53 mutants function as dominant-negative in the nucleus | [57, 58, 143] |
| Retinoblastoma protein (Rb) | Nucleus | Cytoplasm | CDK phosphorylation-dependent nuclear export | Loss of tumor suppressor role | [144, 145] |
| Sirtuin 1 (SIRT1) | Nucleus | Cytoplasm | Deregulation of PI3K/IGF-1R signaling | Loss of tumor suppressor function | [146, 147] |
| Tumor-specific cyclin E isoforms | Nucleus | Cytosol | Deletion of the NLS portion of the aminoterminus | Oncogenic role | [148] |
| V-Erb-B2 Erythroblastic Leukemia Viral Oncogene (ErbB3) | Plasma membrane, Cytoplasm | Nucleus | Bone microenvironment and androgen signaling; alternative transcription initiation producing a functional NLS | Oncogenic role | [149] |
| Mucin-13 | Transmembrane | Cytoplasm, Nucleus | Unclear | Oncogenic role | [150] |
| Inhibitor of Growth Family, Member 1 (ING1/p33) | Nucleus | Cytoplasm | Mutations | Loss of tumor suppressor function | [151] |
| SET-CAN fusion protein | Nucleus | Cytoplasm | Unclear | May be involved in oncogenesis of acute undifferentiated leukemia | [152] |
| Mucin 1 C-terminal (MUC1-C) | Apical membrane | Cytoplasm, Nucleus, Mitochondria | Interaction with β-catenin and EGFR | Oncogenic signal transduction; induce oncogene expression | [32, 95, 153] |
| KL-6 mucin | Cytoplasm, Cell surface | Nucleus | Unclear | Oncogenic role | [154] |
| Epidermal growth factor receptor | Membrane | Cytoplasm, Nucleus | MUC1-dependent, c-Src signaling | Oncogenic signal transduction; induce oncogene expression | [19] |
| Androgen receptor | Cytosol | Nucleus | Nuclear import is facilitated by the f-actin cross-linking protein filamin | Oncogenic role | [155] |
| Nuclear receptor corepressor (N-CoR) | Nucleus | Cytoplasm | Aberrant IKK activation, IKK-induced phosphorylation and binding with 14-3-3 | Loss of tumor suppressor function | [156] |
| Nucleophosmin (NPM1) | Nucleus | Cytosol | Mutations create new NES and impair NLS | Interfere with tumor suppressor ARF | [67, 68, 157] |
| β-Catenin | Membrane | Nucleus, Cytoplasm | Mutations in exon 3 (loss of GSK3β-targeted phosphorylation) | Oncogenic role | [158–161] |
| Adenomatous polyposis coli (APC) | Plasma membrane, Nucleus | Cytoplasm | Mutations; CRM1-dependent nuclear export | Loss of tumor suppressor function; important for colon cancer development | [162, 163] |
| p27 | Nucleus | Cytoplasm | Oncogenic activation of PI3K- and MEK-dependent kinases | Loss of tumor suppressor function | [164, 165] |
| p44/WDR77 | Nucleus | Cytoplasm | Loss of NLS function | Promote proliferation of prostate epithelial cancer cells | [166] |
| E-cadherin | Membrane | Nucleus, Cytoplasm | C-terminal fragment of β-cadherin is translocated into the nucleus by p120 | Loss of tumor suppressor role; induce oncogene expression | [167] [168] |
| ERM Binding Protein 50 (EBP50) | Cytoplasm | Nucleus | Interaction with β-catenin | Oncogenic role; promote colorectal carcinogenesis | [169] |
| Epithelial Cell Adhesion Molecule (EPCAM) | Cell surface | Cytoplasm, Nucleus | Unclear, concomitant with nuclear import of β catenin | A marker for aggressive thyroid cancer and poor prognosis | [170] |
| B7-H1 | Cell surface | Nucleus | Induced by doxorubicin treatment | A possible anti-apoptotic function | [61, 171] |
| B7-H3 | Cell surface | Nucleus | Unclear | Predict poor outcome in colon cancer | [63] |
| B7-H4 | Cell surface | Nucleus | Unclear | promote tumor progression and cell proliferation | [62] |
| Cyclin D1 | Cytosol | Nucleus | KRAS and PIK3CA mutations lead to increased AKT activity and inactivation of GSK3β, loss-of-function mutation of F-box protein 4, and missense mutations in cyclin D1 gene | Oncogenic role | [172–174] |
| Vascular Endothelial Growth Factor Receptor (VEGFR) | Transmembrane | Cytosol, Nucleus | unclear | Angiogenesis; induce VEGFR expression | [175] |