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| Status |
Public on Mar 08, 2023 |
| Title |
A heterodimer of α and β hemoglobin chains functions as an innate anticancer agent |
| Organism |
Homo sapiens |
| Experiment type |
Protein profiling by protein array
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| Summary |
Metastatic (as well as tumor) microenvironments contain both cancer-promoting as well as cancer restraining factors. The balance between these opposing forces determines the fate of cancer cells that disseminate to secondary organ sites. In search for microenvironmental drivers or inhibitors of metastasis, we identified, in a previous study, the beta subunit of hemoglobin (HBB) as a lung-derived antimetastatic factor. In the present study, exploring mechanisms leading to melanoma brain metastasis, we discovered that brain-derived factors restrain proliferation and induce apoptosis and necrosis of brain-metastasizing melanoma cells. Employing various purification procedures, we identified a heterodimer composed of hemoglobin alpha and beta chains that performs these anti-metastatic functions. Neither the alpha nor the beta subunit alone were inhibitory. An alpha/beta chain dimer chemically purified from human hemoglobin inhibited the cell viability of primary melanomas, melanoma brain metastasis (MBM), and breast cancer cell lines. The dimer-induced DNA damage, cell cycle arrest at the SubG1 phase, apoptosis, and significant necrosis in four MBM cell lines. Proteomic analysis of dimer-treated MBM cells revealed that the dimer downregulates the expression of BRD4, GAB2, and IRS2 proteins playing crucial roles in cancer cell sustainability and progression.
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| Overall design |
24 samples ; 4 cell lines, treatment and control for each in triplicates
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| Contributor(s) |
Chelladurai M, Xu D, Izraely S, Bengaiev R, Sagi-Assif O, Yuan W, Pasmanik Chor M, Hoon DS, Lu W, Witz IP |
| Citation missing |
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| Submission date |
Feb 16, 2023 |
| Last update date |
Mar 09, 2023 |
| Contact name |
Metsada Pasmanik-Chor |
| E-mail(s) |
metsada@tauex.tau.ac.il
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| Organization name |
Tel Aviv University
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| Department |
Biology
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| Lab |
Bioinformatics Unit
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| Street address |
Ramat Aviv
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| City |
Tel Aviv |
| ZIP/Postal code |
69978 |
| Country |
Israel |
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| Platforms (1) |
| GPL33134 |
Reverse Phase Protein Array (RPPA) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA935740 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE225459_17_Isaac_Witz_Sivan_Izraely_B.xlsx |
5.8 Mb |
(ftp)(http) |
XLSX |
| Processed data included within Sample table |
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