HIF1A expression in localized prostate cancer treated with dose escalation radiation therapy

Zapatero, A.; Morente, Manuel; Vidales, C. Martín de; Adrados, Magdalena; López, Consuelo; Nieto, Santiago; González, María Jesús Artiga; Arellano, R.; Conde, A. Cruz; Vicente, Feliciano García

doi:10.3233/cbm-140439

Cited by 6 publications

(3 citation statements)

References 13 publications

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“…2d, Supplementary Fig. 2d-e), wherein expected enrichment of circadian regulated factors (CLOCK, BMAL1, E-Box) was complemented by enrichment of cancer-associated transcription factors of PCa relevance, including several with oncogenic activity (e.g., c-Myc, Max, USF1, SP1, ETS factors, HIF-1α) [28][29][30][31][32][33][34] . Additional enriched motifs correspond to components of the FoxA1/AR complex or are directly driven by AR to promote AR signaling, cell proliferation/invasion, metabolic rewiring, and ultimately tumor growth ( Fig.…”

Section: Resultsmentioning

confidence: 97%

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair

et al. 2021

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Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required for homologous recombination. Collectively, these findings reveal that CRY1 is hormone-induced in tumors, is further stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation. These studies identify the circadian factor CRY1 as pro-tumorigenic and nominate CRY1 as a new therapeutic target.

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Section: Resultsmentioning

confidence: 97%

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair

et al. 2021

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“…Particularly, curcumin involves DNA repair pathway mediated by BRCA1 and BRCA2. In other cases, HIF1A functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia 30 ; CFTR functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes 31 ; and glucocorticoids are steroid hormones regulated in a circadian and stress-associated manner to maintain various metabolic and homeostatic functions that are necessary for life 32 . Among them, DNA damage repair is closely related to our findings above.…”

Section: Resultsmentioning

confidence: 99%

Curcumin activates DNA repair pathway in bone marrow to improve carboplatin-induced myelosuppression

Chen

Wang

et al. 2017

Sci Rep

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Carboplatin, a second-generation platinum agent, has been used as a cancer therapy for decades and exhibits strong anti-tumor activity. However, the wide application of carboplatin is largely limited due to its side effects, especially myelosuppression. Here, we combined carboplatin with curcumin, a natural product that improves tumor-induced anemia, for the treatment of fibrosarcoma to improve the side effects of carboplatin. We first examined the synergistic and attenuated effects of the two agents in a T241-bearing mouse model. The combination therapy caused no obvious synergistic effect, but curcumin significantly improved the survival rate of carboplatin-treated mice. Histologic analysis of the kidney and bone marrow revealed that curcumin improved carboplatin-induced myelosuppression but did not affect the kidney. To determine the mechanism involved, we introduced a probe derived from curcumin to identify its targets in bone marrow cells and the results provided us a clue that curcumin might affect the DNA repair pathway. Western blot analysis revealed that curcumin up-regulated BRCA1, BRCA2 and ERCC1 expression in bone marrow. In conclusion, curcumin attenuates carboplatin-induced myelosuppression by activating the DNA repair pathway in bone marrow cells.

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“…The median follow-up time was 10 years. Surprisingly, cytoplasmic overexpression of HIF-1a was associated with the improved overall survival [52].…”

Section: Hypoxia In Prostate Cancermentioning

confidence: 99%

Hypoxia in prostate cancer

Danielska

Łuniewska-Bury²,

Kuncman³

et al. 2017

Nowotwory. Journal of Oncology

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Most human solid tumours contain areas which are less oxygenated than normal tissues. Hypoxia increases resistance to radiotherapy, surgery and chemotherapy, and directly alters the function of tumour cells, stimulating them to de-differentiate and to release angiogenic factors with a view to increasing the blood and oxygen supply. Tumour hypoxia promotes malignant progression and metastasis formation. HIF-1 is a heterodimeric transcription factor composed of regulated HIF-1a and constitutively expressed HIF-1b. Tumour-associated activation of HIF-1a seems to be primarily, however the result of adaptation to oxygen shortage. The presence of the HIF-1a subunit overexpression has been confirmed in many tumours, in prostate cancer, among others; the role it plays in its progression is yet to be explained. Numerous studies strongly emphasize the importance of evaluating the status of the HIF-1a transcription factor in predicting the clinical and biochemical recurrence of prostate cancer and its resistance to castration. NOWOTWORY J Oncol 2017; 67, 2: 132-136

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HIF1A expression in localized prostate cancer treated with dose escalation radiation therapy

Cited by 6 publications

References 13 publications

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair

Curcumin activates DNA repair pathway in bone marrow to improve carboplatin-induced myelosuppression

Hypoxia in prostate cancer

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