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Updated: Jul 3, 2026
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells
Kazuo Kamemura1, Akihiro Ito, Tadahiro Shimazu
1Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.
Abstract:
Histone deacetylase 6 (HDAC6) is a multifunctional, cytosolic protein deacetylase that primarily acts on alpha-tubulin. Here we report that stable knockdown of HDAC6 expression causes a decrease in the steady-state level of receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha, in A549 lung cancer cells. The decreased levels of in EGFR in HDAC6-knockdown cells, which correlated with increased acetylation of microtubules, were due to increased turnover of EGFR protein. Despite the decrease in EGFR levels, A549 cells lacking functional HDAC6 appeared to grow normally, probably due to increased expression of extracellular signal-regulated kinases 1 and 2. Indeed, HDAC6-knockdown cells were more sensitive than control cells to the MEK inhibitor U0126. These results suggest that HDAC6 inhibitors combined with inhibitors of growth factor signaling may be useful as cancer therapy.
Insights
Knocking down histone deacetylase 6 (HDAC6) reduces cancer cell receptor tyrosine kinases, suggesting combination therapies targeting HDAC6 and growth factor signaling may improve cancer treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Histone deacetylase 6 (HDAC6) is a key cytosolic deacetylase.
- HDAC6 primarily deacetylates alpha-tubulin.
- Its role in cancer cell signaling is under investigation.
Purpose of the Study:
- To investigate the effect of HDAC6 knockdown on receptor tyrosine kinases (RTKs) in lung cancer cells.
- To explore the underlying mechanisms of RTK level changes.
- To assess the therapeutic potential of targeting HDAC6 in combination with growth factor signaling inhibitors.
Main Methods:
- Stable knockdown of HDAC6 expression in A549 lung cancer cells.
- Analysis of steady-state levels of epidermal growth factor receptor (EGFR) and other RTKs.
- Assessment of EGFR protein turnover and microtubule acetylation.
- Evaluation of cell growth and sensitivity to MEK inhibitor U0126.
Main Results:
- HDAC6 knockdown decreased steady-state levels of EGFR and other RTKs in A549 cells.
- EGFR degradation increased in HDAC6-knockdown cells, correlating with elevated microtubule acetylation.
- HDAC6-deficient cells exhibited normal growth, potentially due to increased extracellular signal-regulated kinases 1 and 2 (ERK1/2) expression.
- HDAC6-knockdown cells showed increased sensitivity to the MEK inhibitor U0126.
Conclusions:
- HDAC6 regulates RTK stability in lung cancer cells.
- Targeting HDAC6 may enhance the efficacy of growth factor signaling inhibitors in cancer therapy.
- Combination therapy involving HDAC6 inhibitors and growth factor signaling inhibitors shows promise for cancer treatment.
