Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival
It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into t...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1034205/full |
| _version_ | 1797943435726946304 |
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| author | Lakhveer Singh Lakshmi Nair Dinesh Kumar Mandeep Kumar Arora Sakshi Bajaj Manoj Gadewar Shashank Shekher Mishra Santosh Kumar Rath Amit Kumar Dubey Gaurav Kaithwas Manjusha Choudhary Manjari Singh |
| author_facet | Lakhveer Singh Lakshmi Nair Dinesh Kumar Mandeep Kumar Arora Sakshi Bajaj Manoj Gadewar Shashank Shekher Mishra Santosh Kumar Rath Amit Kumar Dubey Gaurav Kaithwas Manjusha Choudhary Manjari Singh |
| author_sort | Lakhveer Singh |
| collection | DOAJ |
| description | It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME. |
| first_indexed | 2024-04-10T20:24:09Z |
| format | Article |
| id | doaj.art-4e6985ddd84e4eacb3248036ccaa23d3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T20:24:09Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4e6985ddd84e4eacb3248036ccaa23d32023-01-25T13:23:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011310.3389/fonc.2023.10342051034205Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survivalLakhveer Singh0Lakshmi Nair1Dinesh Kumar2Mandeep Kumar Arora3Sakshi Bajaj4Manoj Gadewar5Shashank Shekher Mishra6Santosh Kumar Rath7Amit Kumar Dubey8Gaurav Kaithwas9Manjusha Choudhary10Manjari Singh11School of Pharmaceutical & Population Health Informatics, DIT University, Dehradun, IndiaDepartment of Pharmaceutical Science, Assam University (A Central University), Silchar, Assam, IndiaDepartment of Pharmaceutical Sciences, Central University of Haryana, Mahendergarh, Haryana, IndiaSchool of Pharmaceutical & Population Health Informatics, DIT University, Dehradun, IndiaChaudhary Devi Lal College of Pharmacy, Yamuna Nagar, IndiaSchool of Medical and Allied Sciences, KR Mangalam University, Gurgaon, IndiaSchool of Pharmaceutical & Population Health Informatics, DIT University, Dehradun, IndiaSchool of Pharmaceutical & Population Health Informatics, DIT University, Dehradun, IndiaSchool of Pharmaceutical & Population Health Informatics, DIT University, Dehradun, IndiaDepartment of Pharmaceutical Science, Babasaheb Bhimrao Ambedkar University, Lucknow, IndiaUniversity Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, IndiaDepartment of Pharmaceutical Science, Assam University (A Central University), Silchar, Assam, IndiaIt is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.https://www.frontiersin.org/articles/10.3389/fonc.2023.1034205/fullhypoxiaHIF-1αlactateangiogenesisinvasivenessresistance |
| spellingShingle | Lakhveer Singh Lakshmi Nair Dinesh Kumar Mandeep Kumar Arora Sakshi Bajaj Manoj Gadewar Shashank Shekher Mishra Santosh Kumar Rath Amit Kumar Dubey Gaurav Kaithwas Manjusha Choudhary Manjari Singh Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival Frontiers in Oncology hypoxia HIF-1α lactate angiogenesis invasiveness resistance |
| title | Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival |
| title_full | Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival |
| title_fullStr | Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival |
| title_full_unstemmed | Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival |
| title_short | Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival |
| title_sort | hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival |
| topic | hypoxia HIF-1α lactate angiogenesis invasiveness resistance |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1034205/full |
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