Abstract P1-07-16: Galectin-7 increases resistance of breast cancer cells to drug-induced apoptosis and promotes tumor escape by killing T cells
Bibliographic record
Abstract
Abstract Resistance to apoptosis induced by anti-cancer drugs is a major obstacle for the treatment of aggressive forms of breast cancer. Galectin-7 was recently shown to be specifically expressed in basal-like and HER-2 positive but not in luminal subtypes of human breast cancer. Galectin-7 also increases the metastatic behavior of breast cancer cells since overexpression of this protein in poorly metastatic breast cancer cells increases their ability to metastasize to the bone and to the lung. This pro-tumoral activity of galectin-7 in breast cancer is surprising since galectin-7 had been previously associated with activation of p53 and breast cancer cells often harbor a transcriptionally inactive form of p53. We have recently reconcile this apparent contradiction by showing that elevated levels of galectin-7 in breast cancer cells occurs via a gain-of-function mechanism of mutant p53. In p53-null breast cancer cells, we have shown that C/EBPβ-2 (also known as LAP2), the most transcriptionally active of the C/EBPβ isoforms, is responsible for the upregulation of galectin-7. How galectin-7 contributes to the progression of breast cancer remains unclear. Up to now, regulation of apoptosis by intracellular galectins has been largely attributed to their ability to translocate to mitochondria, possibly following their interaction with bcl-2. Here, we report that a mutant of galectin-7 that is unable to translocate to mitochondria induces resistance of human breast cancer cells to apoptosis induced by etoposide or by hypoxia-mimicking conditions. Surprisingly, this mutant and the wild-type form of galectin-7 bind equally well to bcl-2 in vitro and in vivo. Interestingly, both forms decreases the translocation of p53 to the nucleus and reduce the expression of p21 following treatment with doxorubicin. We also found that galectin-7 was released by breast cancer cells and that recombinant galectin-7 increased apoptosis of monocytes, T CD4+ and T CD8+ cells. This suggests that galectin-7 contributes to the establishment of an immunosuppressive tumor microenvironment by killing helper and effector T cells. Taken together, these results challenges the current paradigm that mitochondrial galectins are important for resistance to apoptosis and call for a greater focus on the role of galectin-7 in breast cancer. They also indicate that targeting both cytosolic and extracellular galectin-7 could improve the efficacy of anti-cancer drugs for the treatment of aggressive forms of breast cancer. Citation Format: Yves St-Pierre, Andrée-Anne Grosset, Marilyne Labrie, Donald Gagné, Maria-Claudia Vladoiu, Louis Gaboury, Nicolas Doucet. Galectin-7 increases resistance of breast cancer cells to drug-induced apoptosis and promotes tumor escape by killing T cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-16.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".