The DOI matches its Crossref record; 121 of the 122 references it cites were found in a registry or an index.
HIF-1 in cancer therapy: two decade long story of a transcription factor
Open accessAbstract
Background: Oxygen (O2) homeostasis is an indispensable requirement of eukaryotes. O2 concentration in cellular milieu is defined as normoxia (∼21% O2), physoxia (∼1–13% O2) or hypoxia (∼0.1–1% O2). Hypoxia, a striking micro-environmental feature in tumorigenesis, is countered by tumor cells via induction of O2 governed transcription factor, hypoxia inducible factor-1 (HIF-1). Post discovery, HIF-1 has emerged as a promising anticancer therapeutic target during the last two decades. Recent reports have highlighted that enhanced levels of HIF-1 correlate with tumor metastasis leading to poor patient prognosis.Material and methods: A systematic search in PubMed and SciFinder for the literature on HIF-1 biology and therapeutic importance in cancer was carried out.Results: This review highlights the initial description as well as the recent insights into HIF-1 biology and regulation. We have focused on emerging data regarding varied classes of HIF-1 target genes affecting various levels of crosstalk among tumorigenic pathways. We have emphasized on the fact that HIF-1 acts as a networking hub coordinating activities of multiple signaling molecules influencing tumorigenesis. Emerging evidences indicate role of many HIF-induced proteomic and genomic alterations in malignant progression by mediating a myriad of genes stimulating angiogenesis, anaerobic metabolism and survival of cancer cells in O2-deficient microenvironment.Conclusions: Better understanding of the crucial role of HIF-1 in carcinogenesis could offer promising new avenues to researchers and aid in elucidating various open issues regarding the use of HIF-1 as an anticancer therapeutic target. In spite of large efforts in this field, many questions still remain unanswered. Hence, future investigations are necessary to devise, assess and refine methods for translating previous research efforts into novel clinical practices in cancer treatment.
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“However, no specific HIF inhibitor has been approved for clinical use8.”
From Liposomal Formulation of HIF-1α Inhibitor Echinomycin Eliminates Established Metastases of Triple-negative Breast Cancer (2020) · cites this paper as [8]
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“HIF-1α drives tumor progression because it orchestrates fundamental processes such as angiogenesis, glycolytic switch, and metastasis8.”
From Liposomal Formulation of HIF-1α Inhibitor Echinomycin Eliminates Established Metastases of Triple-negative Breast Cancer (2020) · cites this paper as [8]
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4 retracted
Samanta, D., Gilkes, D. M., Chaturvedi, P., Xiang, L., & Semenza, G. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421438111 · Cited by 460
RetractedRETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
Lee, K., Zhang, H., Qian, D. Z., Rey, S., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909353106 · Cited by 451 · cited 1×
“In vivo investigations revealed that targeting HIF-1 function significantly inhibits tumor vascularization [79].”
BackgroundRetractedZhang, H., Wong, C. C. L., Wei, H., Gilkes, D. M., Korangath, P., Chaturvedi, P., Schito, L., Chen, J., Krishnamachary, B., Winnard, P. T., et al. (2012) · Oncogene · doi:10.1038/onc.2011.365 · Cited by 326
RetractedMaroni, P., Matteucci, E., Drago, L., Banfi, G., Bendinelli, P., & Desiderio, M. A. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.10.004 · Cited by 32
RetractedWang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212 · cited 1×
“HIF-1a, a basic-helix-loop-helix (bHLH)-PER (Period)ARNT-SIM (single minded) (PAS) superfamily member is the O2-labile subunit and is ubiquitously expressed in hypoxia [10].”
BackgroundThe tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180 · cited 1×
“[19] first demonstrated a central role of pVHL in HIF-1a regulation in 1999, and during the next decade mechanistic specifications of pVHL-HIF pathway and regulation of proteasomal degradation and polyubiquitylation were elucidated.”
BackgroundHIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 1×
“Under normal O2 tension, the PHDs become active and cause prolyl hydroxylation in HIF-1, leading to a recognition indicator for pVHL binding, ubiquitylation and subsequent degradation of HIF-1a [33].”
BackgroundSuccinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176 · cited 1×
“HIF-1 serves as an important moderator of the Warburg effect, the tumor-related metabolic switch, which helps cancer cells to create energy largely by disintegration of glucose in a non-oxidative manner rather than typical oxidative phosphorylation [64].”
BackgroundEpstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333 · cited 1×
“are hydroxylated by prolyl-4-hydroxylases (PHDs) [15].”
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
Research works printed but not linked: 5
- Huang Z, 2014, Int J Clin Exp Med, 7, 3344
- Takahashi R, 2003, Oncol Rep, 10, 797
- He GD, 2014, Asia Pac J Clin Nutr, 23, 174
- Pan JG, 2007, Sci STKE, 381, e14
- Zhong H, 1999, Cancer Res, 59, 5830
Cited by
Sorted by citations
Nedeljković, M., & Damjanović, A. (2019) · Cells · doi:10.3390/cells8090957 · Cited by 910
“Since the discovery of HIFs, many inhibitors with diverse modes of action have been identified, but none have progressed to clinical use [119].”
BackgroundThe anti-cancer effect of quercetin: molecular implications in cancer metabolism
Reyes-Farias, M., & Carrasco-Pozo, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133177 · Cited by 689
“In fact, HIF-1α is the primary driver of increased glycolysis and lactate production during hypoxia [35].”
BackgroundThe Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
Zhou, J., Kang, Y., Chen, L., Wang, H., Liu, J., Zeng, S., & Yu, L. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00343 · Cited by 481
“Whereas under hypoxic conditions, impaired hydroxylation process stabilizes the HIF1a protein, furthermore HIF1a will translocate into nuclear and dimerize with HIF1b to transactivate the target genes which relate with glucose metabolism, angiogenesis, cell proliferation, invasion and metastasis (reviewed in Pawlus an…”
BackgroundMarra, A., Trapani, D., Viale, G., Criscitiello, C., & Curigliano, G. (2020) · npj Breast Cancer · doi:10.1038/s41523-020-00197-2 · Cited by 332
HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies
Zhao, Y., Xing, C., Deng, Y., Ye, C., & Peng, H. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.02.039 · Cited by 231
“It has been reported that HIF-1a is highly expressed in tumors such as breast, liver, bladder, cervical, colorectal, endometrial, lung, etc.(77) NANOG is a protein required for the self-renewal of breast cancer stem cells (BCSCs), and high expression of NANOG in tumor tissues of breast cancer patients is correlated wi…”
Background
Metadata
- Authors
- Soni, S., & Padwad, Y. S.
- Affiliations
- Institute of Himalayan Bioresource Technology (IN)
- Corresponding author
- Padwad, Yogendra S.
- Venue
- Acta Oncologica
- Published
- 2017-03-30
- Volume
- 56
- Issue
- 4
- Pages
- 503-515
- ISSN
- 0284-186X (ISSN-L)
- 1651-226X
- OpenAlex
- W2599085091
- Cited by
- 251
- References
- 122
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 16 · 2023: 35 · 2022: 34 · 2021: 38 · 2020: 41 · 2019: 43 · 2018: 20 · 2017: 1
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Acta Oncologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research
- Council for Scientific and Industrial Research (MLP0039)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- HIF-1, tumor hypoxia, oxygen homeostasis, transcription factor regulation, HIF-1 target genes, tumor angiogenesis, anaerobic metabolism, metastasis, carcinogenesis, cancer therapy targets, tumor microenvironment
- MeSH terms
- Animals, Humans, Neoplasms, Cell Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit
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