Protein kinase CK2 sustains de novo fatty acid synthesis by regulating the expression of SCD-1 in human renal cancer cells
Bibliographic record
Abstract
Clear cell renal cell carcinoma (ccRCC) is a type of cancer characterized by a vast intracellular accumulation of lipids that are critical to sustain growth and viability of the cells in the tumour microenvironment. Stearoyl-CoA 9-desaturase 1 (SCD-1) is an essential enzyme for the synthesis of monounsaturated fatty acids and consistently overexpressed in all stages of ccRCC growth. Human clear cell renal cell carcinoma lines were treated with small-molecule inhibitors of protein kinase CK2. Effects on the expression levels of SCD-1 were investigated by RNA-sequencing, RT-qPCR, Western blot, and in vivo studies in mice. Phase-contrast microscopy, fluorescence microscopy, flow cytometry, and MALDI-mass spectrometry analysis were carried out to study the effects on endogenous lipid accumulation, induction of endoplasmic reticulum stress, rescue effects induced by exogenous MUFAs, and the identity of lipid populations. Cell proliferation and survival were investigated in real time employing the Incucyte® live-cell analysis system. Statistical significance was determined by applying the two-tailed Student’s t test when comparing two groups of data whereas the two-way ANOVA, multiple Tukey’s test was employed for multiple comparisons. Here, we show that protein kinase CK2 is critical for preserving the expression of SCD-1 in ccRCC lines maintained in culture and heterotransplanted into nude mice. Consistent with this, pharmacological inhibition of CK2 leads to induction of endoplasmic reticulum stress linked to unfolded protein response activation and decreased proliferation of the cells. Both effects could be reversed by supplementing the growth medium with oleic acid indicating that these effects are specifically caused by reduced expression of SCD-1. Analysis of lipid composition by MALDI-mass spectrometry revealed that inhibition of CK2 results in a significant accumulation of the saturated palmitic- and stearic acids. Collectively, our results revealed a previously unidentified molecular mechanism regulating the synthesis of monounsaturated fatty acids corroborating the notion that novel therapeutic approaches that include CK2 targeting, may offer a greater synergistic anti-tumour effect for cancers that are highly dependent on fatty acid metabolism.
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.
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 | 0.000 | 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 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".