<i>CUL4A</i> contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response

Saucedo-Cuevas, Laura; Ruppen, Isabel; Ximénez-Embún, Pilar; Domingo, Samuel; Gayarre, Javier Machín; Muñoz, Javier; Silva, José M.; García, Maria José; Benı́tez, Javier

doi:10.18632/oncotarget.1915

Cited by 17 publications

(17 citation statements)

References 46 publications

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“…Ten were downregulated in the treated sample, while the other 46 were upregulated. Six of the downregulated genes (PLEC, SYK, STK35, SLC35B2, CUL4a, and EPCAM) are known to facilitate cancer cell invasion and/or extravasation for metastasis 29 30 31 32 33 34 ( Fig. 4D ).…”

Section: Resultsmentioning

confidence: 99%

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Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness

Lee

Evgrafov

Souaiaia

et al. 2015

Sci Rep

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RE1-Silencing Transcription factor (REST) has a well-established role in regulating transcription of genes important for neuronal development. Its role in cancer, though significant, is less well understood. We show that REST downregulation in weakly invasive MCF-7 breast cancer cells converts them to a more invasive phenotype, while REST overexpression in highly invasive MDA-MB-231 cells suppresses invasiveness. Surprisingly, the mechanism responsible for these phenotypic changes does not depend directly on the transcriptional function of REST protein. Instead, it is driven by previously unstudied mid-size (30–200 nt) non-coding RNAs (ncRNAs) derived from the first exon of an alternatively spliced REST transcript: REST-003. We show that processing of REST-003 into ncRNAs is controlled by an uncharacterized serine/arginine repeat-related protein, SRRM3. SRRM3 expression may be under REST-mediated transcriptional control, as it increases following REST downregulation. The SRRM3-dependent regulation of REST-003 processing into ncRNAs has many similarities to recently described promoter-associated small RNA-like processes. Targeting ncRNAs that control invasiveness could lead to new therapeutic approaches to limit breast cancer metastasis.

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Section: Resultsmentioning

confidence: 99%

“…These genes are known to be important not only for cell line invasiveness ( Fig. 4D ), but also for cancer tumor progression to metastasis 29 30 31 32 33 34 . This suggests that REST-003 ultimately plays an important role in controlling invasiveness through a gene expression program.…”

Section: Discussionmentioning

confidence: 99%

Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness

Lee

Evgrafov

Souaiaia

et al. 2015

Sci Rep

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“…Cullin 3 accelerates the progression of breast cancer by regulating the effect of speckle-type POZ protein on the expression of breast cancer metastasis suppressor 1 (7). The overexpression of cullin 4A promotes growth and metastasis of basal-like breast tumors (8). Cullin 7 is one of the structural components of E3 ubiquitin ligases and functions as an oncogene to play a critical role in the proliferation and differentiation of pancreatic cancer cells (9).…”

Section: Introductionmentioning

confidence: 99%

Cullinï¿½7 is a predictor of poor prognosis in breast cancer patients and is involved in the proliferation and invasion of breast cancer cells by regulating the cell cycle and microtubule stability

Qiu

Zhang

et al. 2017

Oncol Rep

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Cullin 7 is the 'scaffold' of the cullin-RING-based E3 ligases which catalyze the final step of the ubiquitination cascade in eukaryotic organisms. Although one study has reported the involvement of cullin 7 in the invasion and migration of breast cancer cells without further exploration of its mechanisms, the expression of cullin 7 in breast cancer tissues and its clinical significance have not been reported. The present study evaluated cullin 7 protein expression in malignant and benign breast tissues using immunochemistry, and further analyzed the association of positive cullin 7 expression in breast cancer tissues with clinicopathological characteristics of breast cancer patients. Cullin 7 expression was further silenced in breast cancer cells by siRNA and its functions and mechanisms in cell proliferation and invasion were investigated. The results showed that high cullin 7 expression was significantly correlated with pathological stage (P=0.013) and lymph node metastasis (P=0.022) of breast cancer. Patients with high cullin 7 expression had a shorter overall survival rate than those with low cullin 7 expression (P=0.037). Silencing of cullin 7 expression significantly inhibited the proliferation (P<0.05) and invasion (P<0.05), increased S1 phase (P<0.05), but decreased G2 phase (P<0.05) in MDA-MB-231 and BT549 cells. In addition, silencing of cullin 7 expression decreased cyclin A, but increased p21 protein expression. Moreover, silencing of cullin 7 expression altered the cell shape, caused disorder in microtubules, and increased the microtubule regeneration in MDA-MB-231 and BT549 cells. In conclusion, cullin 7 is overexpressed in breast cancer tissues which is associated with the development and prognosis of breast cancer. Cullin 7 is involved in the proliferation and invasion of breast cancer cells by regulating the cell cycle and microtubule stability.

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“…IHC staining was used to detect the expression of CUL4A in human OS, indicating increased expression of CUL4A in OS tissues compared to that in the ANCT. transition, and metastasis of breast cancer through regulation of ZEB1 expression and antitumor immune response, 19,20 enhances tumor growth and sensitizes lung cancer cells to erlotinib via regulation of EGFR 21 and determines the response to thalidomide treatment in prostate cancer, 22 involving in the multi-drug resistance in cancer. 23 Inhibition of CUL4A expression can augment DNA damage response and fight against the progression of skin cancer.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of CUL4A inhibits invasion and induces apoptosis in osteosarcoma cells

Song

Zhang

Shao

2015

Int J Immunopathol Pharmacol

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Cullin4A (CUL4A) is implicated in many cellular events including cell survival and growth. However, the specific function and underlying mechanisms of CUL4A in cancer invasion have not yet been elucidated. In this work, we were focused on investigating the role of CUL4A in human osteosarcoma (OS). The expression level of CUL4A was evaluated by immunohistochemical (IHC) assay in human OS tissues. Lentivirus-mediated CUL4A shRNA (Lv-shCUL4A) constructed by us was transfected into OS cells for assessing its effects on cell proliferation and invasive potential, respectively detected by MTT and Transwell assays. It was demonstrated that the expression of CUL4A protein was markedly increased in OS tissues compared with the adjacent non-cancerous tissues (ANCT) (57.8% vs. 25.6%, P = 0.019), and was associated with the distant metastases in OS patients (P = 0.016). In vitro, silencing of CUL4A gene inhibited OS cell proliferation and invasion, and induced cell apoptosis, followed by increased expression of p27 and p53 and decreased expression of MMP-2. Therefore, these findings indicate that elevated expression of CUL4A is positively correlated with distant metastases in OS patients, and knockdown of CUL4A suppresses invasion and induces apoptosis in OS cells, suggesting that CUL4A may serve as a potential target for the treatment of OS.

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CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response

Cited by 17 publications

References 46 publications

Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness

Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness

Cullinï¿½7 is a predictor of poor prognosis in breast cancer patients and is involved in the proliferation and invasion of breast cancer cells by regulating the cell cycle and microtubule stability

Knockdown of CUL4A inhibits invasion and induces apoptosis in osteosarcoma cells

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