The homeobox transcription factor TCF7 is activated in and likely required for metastasis to the lymph nodes in humans with breast cancer.
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2025
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| author | Mamoor, Shahan |
| author_facet | Mamoor, Shahan |
| contents | <p>We describe here one of a series of homeoboxes whose expression is enriched (differentially expressed and activated) in metastasis to the lymph nodes in humans with breast cancer. Metastasis is the major cause of death from cancer (1); metastasis to the lymph nodes in breast cancer is dangerous, relatively common, and in one study ranged from 10-60% based on molecular subtype (2-4). We predict therapeutic index is intrinsically linked to differential expression which can be comprehensively and blindly determined using whole transcriptome data (5). We pioneered understanding of metastasis to the lymph nodes as an intermediate biological and anatomical counterpart to the CNS metastasis in humans (6-12). Here we utilize whole transcriptome technologies (13, 14) to measure total transcription in the lymph node metastases and primary tumors of humans with breast cancer for discovery and insight into clonal evolution through disease progression. We identify here a therapeutic target based on its differential expression and up-regulation upon metastasis to the lymph nodes in humans with breast cancer, TCF7, as a candidate therapeutic target for the medical management of lymph node metastasis. The data which are informed by survival analysis of humans with high and low tumor expression of the homeoboxes described and by study of total transcription following genetic depletion of a selection of these homeoboxes (data not shown) indicate absolute therapeutic efficacy associated with pharmacologic (medical) homeobox inhibition in human cancer, in the primary tumor and in metastasis.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_15190663 |
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| publishDate | 2025 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | The homeobox transcription factor TCF7 is activated in and likely required for metastasis to the lymph nodes in humans with breast cancer. Mamoor, Shahan <p>We describe here one of a series of homeoboxes whose expression is enriched (differentially expressed and activated) in metastasis to the lymph nodes in humans with breast cancer. Metastasis is the major cause of death from cancer (1); metastasis to the lymph nodes in breast cancer is dangerous, relatively common, and in one study ranged from 10-60% based on molecular subtype (2-4). We predict therapeutic index is intrinsically linked to differential expression which can be comprehensively and blindly determined using whole transcriptome data (5). We pioneered understanding of metastasis to the lymph nodes as an intermediate biological and anatomical counterpart to the CNS metastasis in humans (6-12). Here we utilize whole transcriptome technologies (13, 14) to measure total transcription in the lymph node metastases and primary tumors of humans with breast cancer for discovery and insight into clonal evolution through disease progression. We identify here a therapeutic target based on its differential expression and up-regulation upon metastasis to the lymph nodes in humans with breast cancer, TCF7, as a candidate therapeutic target for the medical management of lymph node metastasis. The data which are informed by survival analysis of humans with high and low tumor expression of the homeoboxes described and by study of total transcription following genetic depletion of a selection of these homeoboxes (data not shown) indicate absolute therapeutic efficacy associated with pharmacologic (medical) homeobox inhibition in human cancer, in the primary tumor and in metastasis.</p> |
| title | The homeobox transcription factor TCF7 is activated in and likely required for metastasis to the lymph nodes in humans with breast cancer. |
| url | https://doi.org/10.5281/zenodo.15190663 |