Synergistic inter-clonal cooperation involving crosstalk, co-option and co-dependency can enhance the invasiveness of genetically distant cancer clones
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Despite intensive research, cancer remains a major health problem. The difficulties in treating cancer reflect the complex nature of this disease, including high levels of heterogeneity within tumours. Intra-tumour heterogeneity creates the conditions for inter-clonal competition and selection, which could result in selective sweeps and a reduction in levels of heterogeneity. However, in addition to competing, cancer clones can also cooperate with each other, and the positive effects of these interactions on the fitness of clones could actually contribute to maintaining the heterogeneity of tumours. Consequently, understanding the evolutionary mechanisms and pathways involved in such activities is of great significance for cancer treatment. This is particularly relevant for metastasis (i.e., tumor cell migration, invasion, dispersal and dissemination), which is the most lethal phase during cancer progression. To explore if and how genetically distant clones can cooperate during migration and invasion, this study used three distinct cancer cell lines with different metastatic potentials. RESULTS: We found that (i) the conditioned media from two invasive lines (breast and lung) increased the migration and invasion potential of a poorly metastatic line (breast), and (ii) this inter-clonal cooperative interaction involved the TGF-β1 signalling pathway. Furthermore, when the less aggressive line was co-cultured with the highly metastatic breast line, the invasive potential of both lines was enhanced, and this outcome was dependent on the co-option (through TGF-β1 autocrine-paracrine signalling) of the weakly metastatic clone into expressing an enhanced malignant phenotype that benefited both clones (i.e., a "help me help you" strategy). CONCLUSIONS: Based on our findings, we propose a model in which crosstalk, co-option, and co-dependency can facilitate the evolution of synergistic cooperative interactions between genetically distant clones. Specifically, we suggest that synergistic cooperative interactions can easily emerge, regardless of the degree of overall genetic/genealogical relatedness, via crosstalk involving metastatic clones able to constitutively secrete molecules that induce and maintain their own malignant state (producer-responder clones) and clones that have the ability to respond to those signals (responder clones) and express a synergistic metastatic behaviour. Taking into account the lack of therapies that directly affect the metastatic process, interfering with such cooperative interactions during the early steps in the metastatic cascade could provide additional strategies to increase patient survival.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it