Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient Acquisition
Abstract To grow in nutrient‐deprived tumor microenvironment, cancer cells often internalize and degrade extracellular proteins to refuel intracellular amino acids. However, the nutrient acquisition routes reported by previous studies are mainly restricted in autophagy‐lysosomal pathway. It remains...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202304791 |
| _version_ | 1797365306396508160 |
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| author | Tianyi Wang Yaming Zhang Yuwei Liu Yi Huang Weiping Wang |
| author_facet | Tianyi Wang Yaming Zhang Yuwei Liu Yi Huang Weiping Wang |
| author_sort | Tianyi Wang |
| collection | DOAJ |
| description | Abstract To grow in nutrient‐deprived tumor microenvironment, cancer cells often internalize and degrade extracellular proteins to refuel intracellular amino acids. However, the nutrient acquisition routes reported by previous studies are mainly restricted in autophagy‐lysosomal pathway. It remains largely unknown if other protein degradation systems also contribute to the utilization of extracellular nutrients. Herein, it is demonstrated that under amino acid starvation, extracellular protein internalization through macropinocytosis and protein degradation through ubiquitin‐proteasome system are activated as a nutrient supply route, sensitizing cancer cells to proteasome inhibition. By inhibiting both macropinocytosis and ubiquitin‐proteasome system, an innovative approach to intensify amino acid starvation for cancer therapy is presented. To maximize therapeutic efficacy and minimize systemic side effects, a pH‐responsive polymersome nanocarrier is developed to deliver therapeutic agents specifically to tumor tissues. This nanoparticle system provides an approach to exacerbate amino acid starvation for cancer therapy, which represents a promising strategy for cancer treatment. |
| first_indexed | 2024-03-08T16:48:13Z |
| format | Article |
| id | doaj.art-a31fdb59638f4416a5c0ea484407a273 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T16:48:13Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-a31fdb59638f4416a5c0ea484407a2732024-01-05T08:26:58ZengWileyAdvanced Science2198-38442024-01-01111n/an/a10.1002/advs.202304791Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient AcquisitionTianyi Wang0Yaming Zhang1Yuwei Liu2Yi Huang3Weiping Wang4State Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong ChinaAbstract To grow in nutrient‐deprived tumor microenvironment, cancer cells often internalize and degrade extracellular proteins to refuel intracellular amino acids. However, the nutrient acquisition routes reported by previous studies are mainly restricted in autophagy‐lysosomal pathway. It remains largely unknown if other protein degradation systems also contribute to the utilization of extracellular nutrients. Herein, it is demonstrated that under amino acid starvation, extracellular protein internalization through macropinocytosis and protein degradation through ubiquitin‐proteasome system are activated as a nutrient supply route, sensitizing cancer cells to proteasome inhibition. By inhibiting both macropinocytosis and ubiquitin‐proteasome system, an innovative approach to intensify amino acid starvation for cancer therapy is presented. To maximize therapeutic efficacy and minimize systemic side effects, a pH‐responsive polymersome nanocarrier is developed to deliver therapeutic agents specifically to tumor tissues. This nanoparticle system provides an approach to exacerbate amino acid starvation for cancer therapy, which represents a promising strategy for cancer treatment.https://doi.org/10.1002/advs.202304791amino acid starvationcancer starvation therapymacropinocytosispH‐responsive polymersomesubiquitin‐proteasome system |
| spellingShingle | Tianyi Wang Yaming Zhang Yuwei Liu Yi Huang Weiping Wang Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient Acquisition Advanced Science amino acid starvation cancer starvation therapy macropinocytosis pH‐responsive polymersomes ubiquitin‐proteasome system |
| title | Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient Acquisition |
| title_full | Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient Acquisition |
| title_fullStr | Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient Acquisition |
| title_full_unstemmed | Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient Acquisition |
| title_short | Amino Acid‐Starved Cancer Cells Utilize Macropinocytosis and Ubiquitin‐Proteasome System for Nutrient Acquisition |
| title_sort | amino acid starved cancer cells utilize macropinocytosis and ubiquitin proteasome system for nutrient acquisition |
| topic | amino acid starvation cancer starvation therapy macropinocytosis pH‐responsive polymersomes ubiquitin‐proteasome system |
| url | https://doi.org/10.1002/advs.202304791 |
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