Expression of CREB3L1 blocks key cancer pathways and suppresses metastasis of lung squamous cell carcinoma cells
Bibliographic record
Abstract
Lung cancer is the leading cause of death due to cancer, with higher mortality rates than cancers of the colon, breast and prostate combined. About one quarter of lung cancers are lung squamous cell carcinomas (LUSC), with a five-year survival rate of only 16 %. We discovered that the majority of LUSCs have reduced expression of a key transcription factor CREB3L1 (cAMP responsive element binding protein 3 like 1), known to function as a metastasis suppressor in breast, bladder and ovarian cancers. In this report, we set out to determine if CREB3L1 functions as a metastasis suppressor in LUSCs. A differential gene expression analysis showed that ectopic expression of CREB3L1 in NCI-H2170 and NCI-1703 cells caused significant reductions in many signaling pathway genes involved in promoting cell viability, survival, migration and angiogenesis. Expression of CREB3L1 was able to reduce cell migration and anchorage-independent growth in soft agar in NCI-H2170, NCI-H1703 and NCI-H226 LUSC cells. Expression of CREB3L1 had less impact on the growth of primary xenograft tumors for NCI-H2170 and NCI-H1703 cells, the latter of which formed atypical masses filled with blood. In contrast, xenografts of NCI-H226 expressing CREB3L1 showed significant reductions in primary tumor growth. Finally, in a mouse metastasis assay, expression of CREB3L1 in NCI-H2170 cells significantly reduced the formation of liver metastases and in NCI-H226 cells, lung metastases, as compared to their respective CREB3L1-deficient parental LUSC cells. Taken together, these results strongly support a role for CREB3L1 as a metastasis suppressor in lung squamous cell carcinoma cells. • CREB3L1 expression is lost in most lung squamous cell carcinomas (LUSCs). • Genes differentially expressed in CREB3L1 LUSCs block migration and angiogenesis. • CREB3L1 expression in LUSCs reduces cell migration and growth in soft agar. • CREB3L1 expression in LUSCs blocks metastatic colonization of LUSCs in mice. • CREB3L1 is a metastasis suppressor in LUSC cells.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".