The Target for Statins, HMG-CoA Reductase, Is Expressed in Ductal Carcinoma-In Situ and May Predict Patient Response to Radiotherapy

Butt, Salma; Butt, Talha; Jirström, Karin; Hartman, Linda; Amini, Rose‐Marie; Zhou, Wenjing; Wärnberg, Fredrik; Borgquist, Signe

doi:10.1245/s10434-014-3708-4

Cited by 13 publications

(10 citation statements)

References 27 publications

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“…Overexpression of HMGCR transformed the normal epithelia cells MCF-10A and up-regulation of enzymes in mevalonate pathway was closely correlated with the short survival of the breast cancer patients (Clendening et al, 2010). Moreover, high expression of HMGCR was observed in ductal carcinoma-in-situ, a subtype of breast cancer (Butt et al, 2014). These studies demonstrated the oncogenic roles of HMGCR in the initiation and progression of breast cancer.…”

Section: Discussionmentioning

confidence: 69%

“…Previous studies showed that HMGCR promoted the transformation of normal breast epithelial cells, highlighting the oncogenic roles of HMGCR in the tumorigenesis (Clendening et al, 2010). In addition, the functions of HMGCR in bladder cancer, ductal carcinoma-in-situ (DCIS) breast cancer were found (Butt et al, 2014). In glioblastoma cells, upregulation of HMGCR and other cholesterol biosynthesis genes represented as a novel mechanism for the drug resistance, while inhibiting the HMGCR-mediated cholesterol-mevalonate pathway induced cell cycle arrest and autophagy in U87 glioblastoma cells (Hamm et al, 2014a(Hamm et al, , 2014bRios-Marco et al, 2013.).…”

Section: Introductionmentioning

confidence: 96%

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HMGCR positively regulated the growth and migration of glioblastoma cells

Qiu

Yuan

Chen

et al. 2016

Gene

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 96%

HMGCR positively regulated the growth and migration of glioblastoma cells

Qiu

Yuan

Chen

et al. 2016

Gene

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“…Also, one of the rate-limiting enzyme HMG-CoA reductase has shown the activity of transforming MEF cells [18]. On the other hand, statin, the inhibitors of HMG-CoA reductase, has shown the anti-tumor effects, and the use of statins is associated with reduced cancer-related mortality, which further confirmed the important function of mevalonate pathway in the carcinogenesis [19,20]. Consistently, we have found that SQLE promoted the growth and migration of HCC cells, which further suggested the important function of mevalonate pathway in the progression of HCC.…”

Section: Discussionmentioning

confidence: 83%

Squalene epoxidase (SQLE) promotes the growth and migration of the hepatocellular carcinoma cells

et al. 2015

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Hepatocellular carcinoma (HCC) is one of the most common malignancies with a poor response to chemotherapy. It is very important to identify novel therapeutic targets. Squalene epoxidase (SQLE), one of the rate-limiting enzymes in the cholesterol biosynthesis, recently has been found to be involved in the tumorigenesis. However, its expression profile and function in the progression of HCC remain largely unknown. Here, we found that the expression of SQLE was upregulated in the HCC tissues. Moreover, overexpression of SQLE in HCC cells promoted cell proliferation and migration, while downregulation of SQLE inhibited the tumorigenicity of HCC cells in vitro and in vivo. Mechanistically, SQLE positively regulated the ERK signaling. Taken together, our study suggests that SQLE is a promising therapeutic target in HCC.

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“…The underlying molecular mechanism involved Ras, which confers intrinsic resistance to radiation since in vitro studies using osteosarcoma cells demonstrated that lovastatin decreases this radiation resistance (80,81). Furthermore, HMGCR may serve as a predictive marker of response to postoperative radiotherapy in ductal carcinoma in situ (dCIS) (83). A retrospective cohort study suggested an association between statin therapy and improvement in response of rectal cancer to neoadjuvant chemoradiation (84).…”

Section: Synergism Of Statins With Radiotherapy and Chemotherapymentioning

confidence: 99%

Statins are potential anticancerous agents (Review)

2015

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Abstract. Statins are inhibitors of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR), which is a rate-limiting enzyme in the mevalonate pathway. The pleiotropic effects of statins may be mediated by the inhibition of downstream products such as small GTP-binding proteins, Rho, Ras and Rac whose localization and function are dependent on isoprenylation. Preclinical studies of statins in different cancer cell lines and animal models showed antiproliferative, pro-apoptotic and anti-invasive effects. Notably, statins showed targeted action in cancerous cell lines compared to normal cells. Previous studies have also shown the synergistic effects of statins with chemotherapeutic agents and radiotherapy. This effect of statins was also observed in chemotherapeutic-resistant tumors. Statins were reported to sensitize the cells to radiation by arresting them in the late G1 phase of the cell cycle. Similarly, population-based studies also demonstrated a chemopreventive and survival benefit of statins in various types of cancers. However, this benefit has yet to be proven in clinical trials. The interindividual variation in response to statins may be contributed to many genetic and non-genetic factors, including single-nucleotide polymorphisms in HMGCR gene and the overexpression of heterogeneous nuclear ribonucleoprotein A1, which was reported to reduce HMGCR enzyme activity. However, more studies with large phase III randomized controlled trials in cancer patients should be conducted to establish the effect of statins in cancer prevention and treatment.

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The Target for Statins, HMG-CoA Reductase, Is Expressed in Ductal Carcinoma-In Situ and May Predict Patient Response to Radiotherapy

Cited by 13 publications

References 27 publications

HMGCR positively regulated the growth and migration of glioblastoma cells

HMGCR positively regulated the growth and migration of glioblastoma cells

Squalene epoxidase (SQLE) promotes the growth and migration of the hepatocellular carcinoma cells

Statins are potential anticancerous agents (Review)

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