Dataset Information

Identification of ATP9A interactors in 293T cell line

ABSTRACT: Macropinocytosis is an effective strategy against nutrient starvation, which fuels cancer cells grow in nutrient-limited conditions. However, whether and how macropinocytosis contributes to the rapid proliferation of hepatocellular carcinoma cells that frequently exhibit inadequate nutrient supply remains unclear. Here, we reveal that nutrient starvation strongly induced macropinocytosis in some hepatocellular carcinoma cells, which allowed the cells to acquire extracellular nutrients and support energy supply to maintain rapid proliferation. Furthermore, we determined that the phospholipid flippase ATP9A was critical for regulating macropinocytosis in hepatocellular carcinoma cells and that high ATP9A levels predicted poor prognosis in hepatocellular carcinoma. ATP9A interacted with ATP6V1A and facilitated its transport to the plasma membrane, which promoted plasma membrane cholesterol accumulation and subsequently drove RAC1-dependent macropinocytosis. Importantly, macropinocytosis inhibitors significantly suppressed the energy supply and proliferation in hepatocellular carcinoma cells characterized by high ATP9A expression under nutrient-limited conditions. These results revealed a novel route to overcome nutrient starvation in hepatocellular carcinoma cells and identify the key regulator of macropinocytosis in hepatocellular carcinoma.

ORGANISM(S): Homo Sapiens

SUBMITTER: Guan Jian

PROVIDER: PXD038797 | iProX | Tue Dec 13 00:00:00 GMT 2022

REPOSITORIES: iProX

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Publications

The phospholipid flippase ATP9A enhances macropinocytosis to promote nutrient starvation tolerance in hepatocellular carcinoma.

Wang Xiaoqing X Li Yue Y Xiao Yunyun Y Huang Xinjian X Wu Xianqiu X Zhao Zhen Z Yang Muwen M Kong Lingzhi L Shi Dongni D Chen Xin X Ouyang Ying Y Chen Xiangfu X Lin Chuyong C Li Jun J Song Libing L Lin Ye Y Guan Jian J

The Journal of pathology 20230228 1

Macropinocytosis is an effective strategy to mitigate nutrient starvation. It can fuel cancer cell growth in nutrient-limited conditions. However, whether and how macropinocytosis contributes to the rapid proliferation of hepatocellular carcinoma cells, which frequently experience an inadequate nutrient supply, remains unclear. Here, we demonstrated that nutrient starvation strongly induced macropinocytosis in some hepatocellular carcinoma cells. It allowed the cells to acquire extracellular nut ...[more]

PMID: 36715683

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Project description:Cultivation methods used to investigate microbial calorie restriction often result in carbon and energy starvation. This study aims to dissect cellular responses to calorie restriction and starvation in Saccharomyces cerevisiae by using retentostat cultivation. In retentostats, cells are continuously supplied with a small, constant carbon and energy supply, sufficient for maintenance of cellular viability and integrity but insufficient for growth. When glucose-limited retentostats cultivated under extreme calorie restriction were subjected to glucose starvation, calorie-restricted and glucose-starved cells were found to share characteristics such as increased heat-shock tolerance and expression of quiescence-related genes. However, they also displayed strikingly different features. While calorie-restricted yeast cultures remained metabolically active and viable for prolonged periods of time, glucose starvation resulted in rapid consumption of reserve carbohydrates, population heterogeneity due to appearance of senescent cells and, ultimately, loss of viability. Moreover, during starvation, calculated rates of ATP synthesis from storage carbohydrates were 2-3 orders of magnitude lower than steady-state ATP-turnover rates calculated under extreme calorie restriction in retentostats. Stringent reduction of ATP turnover during glucose starvation was accompanied by a strong down-regulation of genes involved in protein synthesis. These results demonstrate that extreme calorie restriction and carbon starvation represent different physiological states in S. cerevisiae. The yeast was first grown for 14 days under extreme calorie restriction in anaerobic, glucose-limited retentostats (Boender et al., 2009, Appl.Environ.Microbiol., 75: 5607-5614.). Subsequently, starvation was started by terminating the glucose feed. Yeast transcriptional reprogramming in response to calorie restriction and starvation was monitored by microarray analysis. Independent duplicate retentostat cultures, and subsequently starvation, were sampled for transcriptome analysis using Affymetrix microarrays. One time-point was sampled during calorie restriction (T0) and four time points were sampled during the starvation phase 10, 30, 60 and 120 minutes after switching of the feed, resulting in a dataset of 10 arrays.

Dataset Information

Identification of ATP9A interactors in 293T cell line

Publications

The phospholipid flippase ATP9A enhances macropinocytosis to promote nutrient starvation tolerance in hepatocellular carcinoma.

Similar Datasets

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