Nutritional Niches of Cancer Therapy-Induced Senescent Cells
Therapy-induced senescence (TIS) is a state of stable proliferative arrest of both normal and neoplastic cells that is triggered by exposure to anticancer treatments. TIS cells acquire a senescence-associated secretory phenotype (SASP), which is pro-inflammatory and actively promotes tumor relapse a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/17/3636 |
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| author | Àngela Llop-Hernández Sara Verdura Elisabet Cuyàs Javier A. Menendez |
| author_facet | Àngela Llop-Hernández Sara Verdura Elisabet Cuyàs Javier A. Menendez |
| author_sort | Àngela Llop-Hernández |
| collection | DOAJ |
| description | Therapy-induced senescence (TIS) is a state of stable proliferative arrest of both normal and neoplastic cells that is triggered by exposure to anticancer treatments. TIS cells acquire a senescence-associated secretory phenotype (SASP), which is pro-inflammatory and actively promotes tumor relapse and adverse side-effects in patients. Here, we hypothesized that TIS cells adapt their scavenging and catabolic ability to overcome the nutritional constraints in their microenvironmental niches. We used a panel of mechanistically-diverse TIS triggers (i.e., bleomycin, doxorubicin, alisertib, and palbociclib) and Biolog Phenotype MicroArrays to identify (among 190 different carbon and nitrogen sources) candidate metabolites that support the survival of TIS cells in limiting nutrient conditions. We provide evidence of distinguishable TIS-associated nutrient consumption profiles involving a core set of shared (e.g., glutamine) and unique (e.g., glucose-1-phosphate, inosine, and uridine) nutritional sources after diverse senescence-inducing interventions. We also observed a trend for an inverse correlation between the intensity of the pro-inflammatory SASP provoked by different TIS agents and diversity of compensatory nutritional niches utilizable by senescent cells. These findings support the detailed exploration of the nutritional niche as a new metabolic dimension to understand and target TIS in cancer. |
| first_indexed | 2024-03-10T01:23:51Z |
| format | Article |
| id | doaj.art-6871b7576ba84deba83a09241728ecc1 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T01:23:51Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-6871b7576ba84deba83a09241728ecc12023-11-23T13:53:46ZengMDPI AGNutrients2072-66432022-09-011417363610.3390/nu14173636Nutritional Niches of Cancer Therapy-Induced Senescent CellsÀngela Llop-Hernández0Sara Verdura1Elisabet Cuyàs2Javier A. Menendez3Girona Biomedical Research Institute, 17190 Girona, SpainMetabolism and Cancer Group, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, 17005 Girona, SpainGirona Biomedical Research Institute, 17190 Girona, SpainGirona Biomedical Research Institute, 17190 Girona, SpainTherapy-induced senescence (TIS) is a state of stable proliferative arrest of both normal and neoplastic cells that is triggered by exposure to anticancer treatments. TIS cells acquire a senescence-associated secretory phenotype (SASP), which is pro-inflammatory and actively promotes tumor relapse and adverse side-effects in patients. Here, we hypothesized that TIS cells adapt their scavenging and catabolic ability to overcome the nutritional constraints in their microenvironmental niches. We used a panel of mechanistically-diverse TIS triggers (i.e., bleomycin, doxorubicin, alisertib, and palbociclib) and Biolog Phenotype MicroArrays to identify (among 190 different carbon and nitrogen sources) candidate metabolites that support the survival of TIS cells in limiting nutrient conditions. We provide evidence of distinguishable TIS-associated nutrient consumption profiles involving a core set of shared (e.g., glutamine) and unique (e.g., glucose-1-phosphate, inosine, and uridine) nutritional sources after diverse senescence-inducing interventions. We also observed a trend for an inverse correlation between the intensity of the pro-inflammatory SASP provoked by different TIS agents and diversity of compensatory nutritional niches utilizable by senescent cells. These findings support the detailed exploration of the nutritional niche as a new metabolic dimension to understand and target TIS in cancer.https://www.mdpi.com/2072-6643/14/17/3636senescencemetabolismglutaminenutritioncancermiR146a |
| spellingShingle | Àngela Llop-Hernández Sara Verdura Elisabet Cuyàs Javier A. Menendez Nutritional Niches of Cancer Therapy-Induced Senescent Cells Nutrients senescence metabolism glutamine nutrition cancer miR146a |
| title | Nutritional Niches of Cancer Therapy-Induced Senescent Cells |
| title_full | Nutritional Niches of Cancer Therapy-Induced Senescent Cells |
| title_fullStr | Nutritional Niches of Cancer Therapy-Induced Senescent Cells |
| title_full_unstemmed | Nutritional Niches of Cancer Therapy-Induced Senescent Cells |
| title_short | Nutritional Niches of Cancer Therapy-Induced Senescent Cells |
| title_sort | nutritional niches of cancer therapy induced senescent cells |
| topic | senescence metabolism glutamine nutrition cancer miR146a |
| url | https://www.mdpi.com/2072-6643/14/17/3636 |
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