Lamin A/C: Function in Normal and Tumor Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Lamin Proteins
3. Lamin A/C: Gene, Protein, and Nuclear Lamina Structure
4. Lamin A/C: Role in Structural Stability
5. Lamin A/C: Role in Mechanosensing, Mechanosignalling, and Cell Movement
6. Lamin A/C: Role in Genomic Organization and Stability
7. Lamin A/C: Role in Gene Expression and Regulation
8. Lamin A/C in Disease and Cancer
8.1. Laminopathies
8.2. Cancer
9. Deregulated Lamin A/C Expression in Cancer Cells
10. Nuclear Morphology and Cancer
11. Cell Motility/Migration and Cancer
12. Cell Differentiation and Cancer
13. Lamin A/C: Genomic Instability and Senescence in Cancer
14. Lamin A/C Binding Partners and Cancer
15. Prostate Cancer
16. Deregulation of Lamin A/C and Interactive Partners in Prostate Cancer
17. Lamin A/C: Role in Genomic Organization, Expression, and Instability in Prostate Cancer
18. Conclusions
Funding
Conflicts of Interest
References
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Cell and Cancer Type | Lamin A/C Expression | Effect on Cancer | Reference |
---|---|---|---|
Lung cancer cell lines A549, and H1299 | Decrease in lamin A/C | Increased tumor senescence | [73] |
Human non-small cell lung carcinoma H 1299, human osteosarcoma U-2 OS, human cervix carcinoma HeLa | Lamin A/C mutated to S22A-progerin | Increased cellular senescence | [74] |
Breast adenocarcinoma cell lines MDA-MB-231 and MDA-MB-468 | Lamin A/C knockout | Decreased cell’s resistance to fluid shear stress | [75] |
Human pre-metastatic colon adenocarcinoma cell line SW480 | Transfected with GFP-lamin A | Downregulated E-cadherin and increased cell motility | [76] |
Human pre-metastatic colon adenocarcinoma cell line SW480 | Lamin A/C upregulated | Increased cell motility | [65] |
Human ovarian cancer cell line H08910 | Lamin A/C overexpressed, Lamin A/C 30–40% inhibited, lamin A/C 70–80% inhibited | Lamin A/C overexpressed: Decreased migration through 3 μm pore. 30–40% inhibited: Increased migration through 3 μm pore. 70–80% inhibited: Decreased migration through 3 μm pore | [77] |
Prostate cancer cell line DU145 and breast cancer cell line BT-549 | Lamin A/C depleted | Emerin mislocalized and nuclear membrane had blebbing | [78] |
Neuroblastoma cell line SH-SY5Y | Lamin A/C downregulated | Tumor initiating cells developed | [79] |
Breast cancer cell line MDA-MB-231 in suspension culture | Lamin A/C downregulated | Decreased adhesion and reattachment of cells | [80] |
Prostate cancer cell line PC3, DU145, and LNCaP | Lamin A/C upregulated | Increased PI3k subunit, p110, and p85 expression and increased growth and invasive capabilities | [81] |
Prostate cancer cell line PC-3M-1E8 and PC-3M-2B4 | Lamin A/C knockdown | Cell growth was inhibited and colony formation was decreased. E-cadherin downregulated. Vimentin, snail, and slug upregulated | [82] |
Cancer Type | Lamin A/C Expression | Reference |
56 invasive ductal carcinoma samples | Majority of samples heterogeneous for lamin A/C expression, 38% had no lamin A/C expressed | [83] |
656 colorectal adenocarcinoma tumor samples | 70% positive for lamin A/C, 30% negative | [76] |
73 breast cancer tumor samples | 84.9% had low lamin A/C expression (low defined as less than 50% of cancer cells stained positive for lamin A/C) | [84] |
33 small cell lung carcinomas (SCLC), 72 non-small cell lung carcinomas (34 adenocarcinoma, 30 squamous cell carcinoma, 8 large cell carcinoma) | 91% of SCLC had negative or low lamin A/C expression, 3% of non-SCLC had negative or low lamin A/C expression | [85] |
115 breast cancer tissue samples | Lower lamin A/C than found in non-cancerous breast tissue. | [86] |
126 gastric carcinoma samples | 70 positive for lamin A/C 56 negative for lamin A/C (lamin A/C associated with poorer prognosis and lower differentiation) | [87] |
87 endometrial cancer samples | Lamin A was reduced in all high-grade endometrial cancer samples | [88] |
61 epithelial ovarian cancer samples | Lower lamin A expression than normal and benign controls | [70] |
17 primary colorectal carcinomas, 18 adenomatous polyps | Lamin A/C reduced or absent in all samples | [66] |
128 breast adenocarcinomas | Lamin C expression increased, Lamin A expression decreased | [71] |
76 cervical uterine smears (CUS) | 39% normal expression, 28% weak, 33% none. Oncogenic HPV infection rate highest in group with no lamin A/C staining. | [89] |
219 stage II and 151 stage III colon cancer samples | 17.8% low lamin A/C expression, Reoccurrence of cancer 45.5% in low lamin A/C expression group compared to 29.6% in high lamin A/C expression group | [90] |
94 prostate tumor tissue microarrays | Lamin A/C had low expression in tumor regions with a Gleason pattern (GP) less than 3 and higher expression in regions with a GP of 4 or 5 | [81] |
4 prostate adenocarcinoma cohorts | Lamin A/C mRNA reduced when the Gleason score is 8, but the level increases above Gleason score 8 and in metastatic regions | [82] |
Tissue microarray from 501 prostate cancer patients | Low lamin A/C associated with increased lymph node metastasis and disease-specific death | [7] |
Tissue cores from 94 prostate tumor samples | Lamin A expression higher in higher Gleason score tumors | [91] |
Biopsies from 9 patients with Hodgkin’s disease | Most Reed-Sternberg and Hodgkin cells expressed lamin A/C while surrounding B and T lymphocytes did not. | [92] |
Cancer Type | Lamin A/C Expression | Effect on Cancer | Reference |
---|---|---|---|
Invasive breast carcinoma | Reduced lamin A/C expression | More aggressive phenotype than tumors with high lamin A/C expression | [93] |
Stage II and Stage III colon cancer tumors | Low lamin A/C expression | Increased disease recurrence | [90] |
Colorectal adenocarcinoma tumors | Sample either did or did not express lamin A/C | Mortality risk twice as high as tumors not expressing lamin A/C | [76] |
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Dubik, N.; Mai, S. Lamin A/C: Function in Normal and Tumor Cells. Cancers 2020, 12, 3688. https://doi.org/10.3390/cancers12123688
Dubik N, Mai S. Lamin A/C: Function in Normal and Tumor Cells. Cancers. 2020; 12(12):3688. https://doi.org/10.3390/cancers12123688
Chicago/Turabian StyleDubik, Niina, and Sabine Mai. 2020. "Lamin A/C: Function in Normal and Tumor Cells" Cancers 12, no. 12: 3688. https://doi.org/10.3390/cancers12123688