Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380

Huang, Xiao; Cao, Ming; Wang, Li; Wu, Shuhong; Li, Xiaoying; Li, Hongyu; Zhang, Hui; Wang, Rui Yu; Sun, Xiaoping; Wei, Caimiao; Baggerly, Keith A.; Roth, Jack A.; Wang, Michael; Swisher, Stephen G.; Fang, Bingliang

doi:10.18632/oncotarget.2814

Cited by 11 publications

(17 citation statements)

References 59 publications

(82 reference statements)

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“…Because crosstalk and feedback activations are commonly observed in RAS-mediated signaling pathways, and because most solid tumors carry multiple concomitantly activated oncogenes or inactivated tumor suppressor genes [181], simultaneously targeting multiple cancer-associated pathways is likely required for effective anti-RAS therapy. Our experience with selective cell killing of NSC743380 in SULT1A1 + cells [126] indicates that even though some passenger mutations in tumor cells may not contribute to tumorigenesis, they may have an impact on treatment response because of altered drug metabolism. Therefore, they may be used as biomarkers to identify responders.…”

Section: Discussionmentioning

confidence: 99%

“…Our recent study revealed that the expression of a sulfotransferase (SULT), SULT1A1, in cancer cells is required for NSC743380's anticancer activity and that the expression of SULT1A1 is capable of predicting the responses to NSC743380 [126]. SULT1A1 is a biotransformation enzyme that bioactivates several pro-carcinogens [127][128][129][130][131][132][133] and some anticancer drugs, such as tamoxifen [134].…”

Section: Treatment Response In Ras Mutant Human Cancer Cellsmentioning

confidence: 99%

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RAS signaling and anti-RAS therapy: lessons learned from genetically engineered mouse models, human cancer cells, and patient-related studies

Fang¹

2016

ABBS

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Activating mutations of oncogenic RAS genes are frequently detected in human cancers. The studies in genetically engineered mouse models (GEMMs) reveal that Kras-activating mutations predispose mice to early onset tumors in the lung, pancreas, and gastrointestinal tract. Nevertheless, most of these tumors do not have metastatic phenotypes. Metastasis occurs when tumors acquire additional genetic changes in other cancer driver genes. Studies on clinical specimens also demonstrated that KRAS mutations are present in premalignant tissues and that most of KRAS mutant human cancers have co-mutations in other cancer driver genes, including TP53, STK11, CDKN2A, and KMT2C in lung cancer; APC, TP53, and PIK3CA in colon cancer; and TP53, CDKN2A, SMAD4, and MED12 in pancreatic cancer. Extensive efforts have been devoted to develop therapeutic agents that target enzymes involved in RAS posttranslational modifications, that inhibit downstream effectors of RAS signaling pathways, and that kill RAS mutant cancer cells through synthetic lethality. Recent clinical studies have revealed that sorafenib, a pan-RAF and VEGFR inhibitor, has impressive benefits for KRAS mutant lung cancer patients. Combination therapy of MEK inhibitors with either docetaxel, AKT inhibitors, or PI3K inhibitors also led to improved clinical responses in some KRAS mutant cancer patients. This review discusses knowledge gained from GEMMs, human cancer cells, and patient-related studies on RAS-mediated tumorigenesis and anti-RAS therapy. Emerging evidence demonstrates that RAS mutant cancers are heterogeneous because of the presence of different mutant alleles and/or co-mutations in other cancer driver genes. Effective subclassifications of RAS mutant cancers may be necessary to improve patients' outcomes through personalized precision medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Treatment Response In Ras Mutant Human Cancer Cellsmentioning

confidence: 99%

RAS signaling and anti-RAS therapy: lessons learned from genetically engineered mouse models, human cancer cells, and patient-related studies

Fang¹

2016

ABBS

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“…Various endogenous and exogenous compounds in the body are metabolized by the sulfonation process, which is generally initiated by sulfotransferases [1,2]. Among the members in the sulfotransferase family, SULT1 isoform SULT1A1 (Sulfotransferase under the Family of 1A Member 1) is the most abundant and distributed throughout different tissues [3,4].…”

Section: Introductionmentioning

confidence: 99%

Structural and Dynamic Characterizations Highlight the Deleterious Role of SULT1A1 R213H Polymorphism in Substrate Binding

Dash

Ali

Dash

et al. 2019

IJMS

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Sulfotransferase 1A1 (SULT1A1) is responsible for catalyzing various types of endogenous and exogenous compounds. Accumulating data indicates that the polymorphism rs9282861 (R213H) is responsible for inefficient enzymatic activity and associated with cancer progression. To characterize the detailed functional consequences of this mutation behind the loss-of-function of SULT1A1, the present study deployed molecular dynamics simulation to get insights into changes in the conformation and binding energy. The dynamics scenario of SULT1A1 in both wild and mutated types as well as with and without ligand showed that R213H induced local conformational changes, especially in the substrate-binding loop rather than impairing overall stability of the protein structure. The higher conformational changes were observed in the loop3 (residues, 235-263), turning loop conformation to A-helix and B-bridge, which ultimately disrupted the plasticity of the active site. This alteration reduced the binding site volume and hydrophobicity to decrease the binding affinity of the enzyme to substrates, which was highlighted by the MM-PBSA binding energy analysis. These findings highlight the key insights of structural consequences caused by R213H mutation, which would enrich the understanding regarding the role of SULT1A1 mutation in cancer development and also xenobiotics management to individuals in the different treatment stages. of sulfonate (SO 3 − ) group enhances the substrate hydrophilic potentiality or polarity and generates less toxic metabolites, and finally facilitates them for excretion [5,11]. In some cases, sulfonation of exogenous compounds turns them into active mutagens and carcinogens [12][13][14], although it sometimes acts as a chemical defense mechanism against xenobiotics [15].Recently, mutation at 213 positions of SULT1A1 exon 7 (rs9282861) [16,17] was reported by multiple studies to be involved in breast cancer progression [18], especially among the postmenopausal Asian women [19,20]. A meta-analysis showed that polymorphic rs9282861 has a significant association with bladder cancer [21], while a small scale case-control study found a significant association with the prevalence of intestinal cancer [22]. The significant association was also found for developing head and neck cancer [23], lung cancer [11,17,24], and also accountable for acute leukemia in infants and acute myeloid leukemia [25]. Patients having rs9282861 mutation, which caused the change of an amino acid from arginine to histidine at the 213th position (R213H), may have a higher susceptibility for developing esophageal cancer, due to the lower enzymatic activity and thermal stability that affect the procarcinogens metabolisms [4,8,26,27], including various steroid hormones, neurotransmitters, and non-opiateanalgesics [28,29]. Furthermore, the substitution occurred with amino acid having the same side chain polarity, although the mutation was reported to reduce the binding affinity of various substrates, as well as their pharmacokinetic properties [2...

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“…Recently, phase I clinical trials of aminoflavone (5-amino-2,3-fluorophenyl-6,8-difluoro-7-methyl-4H-1-benzopyran-4-1) have been completed, which is believed to function in a similar manner to 5F203. However, recent studies have shown that aminoflavone requires sulfotransferase A1 (SULTA1) expression for a cellular response [109].…”

Section: Natural Compoundsmentioning

confidence: 99%

The Multifarious Link between Cytochrome P450s and Cancer

Alzahrani

2020

Oxidative Medicine and Cellular Longevity

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Cancer is a leading cause of death worldwide. Cytochrome P450s (P450s) play an important role in the metabolism of endogenous as well as exogenous substances, especially drugs. Moreover, many P450s can serve as targets for disease therapy. Increasing reports of epidemiological, diagnostic, and clinical research indicate that P450s are enzymes that play a major part in the formation of cancer, prevention, and metastasis. The purposes of this review are to shed light on the current state of knowledge about the cancer molecular mechanism involving P450s and to summarize the link between the cancer effects and the participation of P450s.

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Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380

Cited by 11 publications

References 59 publications

RAS signaling and anti-RAS therapy: lessons learned from genetically engineered mouse models, human cancer cells, and patient-related studies

RAS signaling and anti-RAS therapy: lessons learned from genetically engineered mouse models, human cancer cells, and patient-related studies

Structural and Dynamic Characterizations Highlight the Deleterious Role of SULT1A1 R213H Polymorphism in Substrate Binding

The Multifarious Link between Cytochrome P450s and Cancer

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