SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity

Liu, Huiquan; Ertay, Ayse; Peng, Ping; Li, Juanjuan; Liu, Dian; Xiong, Hua; Zou, Yanmei; Qian, Hong; Hancock, David C.; Yuan, Xianglin; Huang, Wei-Chien; Ewing, Rob M.; Downward, Julian; Wang, Yihua

doi:10.1002/1878-0261.12530

Cited by 27 publications

(18 citation statements)

References 49 publications

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“…FDG uptake in malignant tumors was mediated by Glucose transportase-1 (GLUT-1) 27 , Higashi et al 28 proposed the correlations between GLUT-1 expression and FDG uptake in NSCLC. EGFR, on the other hand, has a strong interaction with sodium/glucose cotransporter 1 (SGLT1) in various tumors 29 - 31 . As SGLT1 opposed to GLUT-1 27 , this mechanism may partly explaine less FDG avid in EGFR mutations.…”

Section: Discussionmentioning

confidence: 99%

Value of combining PET/CT and clinicopathological features in predicting EGFR mutation in Lung Adenocarcinoma with Bone Metastasis

Yao

Zhou

et al. 2020

J. Cancer

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Purpose: Epidermal growth factor receptor (EGFR) mutation is the most common target for precision treatment in metastatic lung adenocarcinoma. We investigated the predictive role of 18 F-FDG PET/CT and clinicopathological features for EGFR mutations in lung adenocarcinoma with bone metastasis. Methods: Seventy-five lung adenocarcinoma patients with histologically confirmed bone metastasis were included. They all received EGFR status test and PET/CT before systemic treatment. The differences of maximum standardized uptake value (SUVmax) in primary tumor (pSUVmax), regional lymph node (nSUVmax) and bone metastasis (bmSUVmax) between different EGFR status groups were compared, alongside with common clinicopathological features. Multivariate logistic regression analysis was performed to evaluate predictors of EGFR mutations. Results: EGFR mutations were found in 37 patients (49.3%). EGFR mutations were more common in females, non-smokers, expression of Thyroid Transcription Factor-1 (TTF-1) and NaspinA. Low bmSUVmax was significantly associated with EGFR mutations, while no significant difference was observed in pSUVmax and nSUVmax. Multivariate analysis showed that bmSUVmax ≤7, non-smoking, expression of TTF-1 were predictors of EGFR mutations. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.84 for the combination of the three factors. Conclusion: Low bmSUVmax is more frequently in EGFR mutations, and bmSUVmax is an independent predictor of EGFR mutations. Combining bmSUVmax with other clinicopathological features could forecast the EGFR status in lung adenocarcinoma with unavailable EGFR gene testing.

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Section: Discussionmentioning

confidence: 99%

Value of combining PET/CT and clinicopathological features in predicting EGFR mutation in Lung Adenocarcinoma with Bone Metastasis

Yao

Zhou

et al. 2020

J. Cancer

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“…Sodium/glucose co-transporter 1 (SGLT1) is essential for maintaining intracellular glucose concentration and can promote tumor growth by interacting with the epidermal growth factor receptor (EGFR) [ 86 ]. In vitro and in vivo analysis of SGTL1 transporter showed an important link between SGLT1-EGFR, regulating TNBC cell survival.…”

Section: Glycolytic Pathway Targeted By Classical Anticancer Drugsmentioning

confidence: 99%

“…In vitro and in vivo analysis of SGTL1 transporter showed an important link between SGLT1-EGFR, regulating TNBC cell survival. mRNA analysis of this transporter in BC tissue samples indicated the highest expression in TNBC and HER2+ than in luminal A or luminal B [ 86 ]. The same research group also showed that knockdown of SGLT1 significantly reduced TNBC proliferation and tumor size.…”

Section: Glycolytic Pathway Targeted By Classical Anticancer Drugsmentioning

confidence: 99%

Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer

Varghese

Samuel

Líšková

et al. 2020

Cancers

143

101

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Breast cancer (BC) is the most prevalent cancer in women. BC is heterogeneous, with distinct phenotypical and morphological characteristics. These are based on their gene expression profiles, which divide BC into different subtypes, among which the triple-negative breast cancer (TNBC) subtype is the most aggressive one. The growing interest in tumor metabolism emphasizes the role of altered glucose metabolism in driving cancer progression, response to cancer treatment, and its distinct role in therapy resistance. Alterations in glucose metabolism are characterized by increased uptake of glucose, hyperactivated glycolysis, decreased oxidative phosphorylation (OXPHOS) component, and the accumulation of lactate. These deviations are attributed to the upregulation of key glycolytic enzymes and transporters of the glucose metabolic pathway. Key glycolytic enzymes such as hexokinase, lactate dehydrogenase, and enolase are upregulated, thereby conferring resistance towards drugs such as cisplatin, paclitaxel, tamoxifen, and doxorubicin. Besides, drug efflux and detoxification are two energy-dependent mechanisms contributing to resistance. The emergence of resistance to chemotherapy can occur at an early or later stage of the treatment, thus limiting the success and outcome of the therapy. Therefore, understanding the aberrant glucose metabolism in tumors and its link in conferring therapy resistance is essential. Using combinatory treatment with metabolic inhibitors, for example, 2-deoxy-D-glucose (2-DG) and metformin, showed promising results in countering therapy resistance. Newer drug designs such as drugs conjugated to sugars or peptides that utilize the enhanced expression of tumor cell glucose transporters offer selective and efficient drug delivery to cancer cells with less toxicity to healthy cells. Last but not least, naturally occurring compounds of plants defined as phytochemicals manifest a promising approach for the eradication of cancer cells via suppression of essential enzymes or other compartments associated with glycolysis. Their benefits for human health open new opportunities in therapeutic intervention, either alone or in combination with chemotherapeutic drugs. Importantly, phytochemicals as efficacious instruments of anticancer therapy can suppress events leading to chemoresistance of cancer cells. Here, we review the current knowledge of altered glucose metabolism in contributing to resistance to classical anticancer drugs in BC treatment and various ways to target the aberrant metabolism that will serve as a promising strategy for chemosensitizing tumors and overcoming resistance in BC.

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“…After incubation with secondary goat anti-rabbit immunoglobulin conjugated to peroxidaselabelled dextran polymer (SV0002; Boster) at 37°C for 1 h, visualisation, counterstaining with haematoxylin and mounting were performed. Semi-quantitative evaluations of protein expression were scored on the basis of the intensity and the percentage of WDHD1-positive tumour cells as previously described [59][60][61][62] .…”

Section: Immunohistochemical and H/e Staining And Scoringmentioning

confidence: 99%

WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer

Ertay

Liu

et al. 2020

Cell Death Dis

Self Cite

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Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, making it difficult to target therapeutically. Targeting synthetic lethality is an alternative approach for cancer treatment. TNBC shows frequent loss of phosphatase and tensin homologue (PTEN) expression, which is associated with poor prognosis and treatment response. To identify PTEN synthetic lethal interactions, TCGA analysis coupled with a whole-genome siRNA screen in isogenic PTEN-negative and -positive cells were performed. Among the candidate genes essential for the survival of PTEN-inactive TNBC cells, WDHD1 (WD repeat and high-mobility group box DNA-binding protein 1) expression was increased in the low vs. high PTEN TNBC samples. It was also the top hit in the siRNA screen and its knockdown significantly inhibited cell viability in PTEN-negative cells, which was further validated in 2D and 3D cultures. Mechanistically, WDHD1 is important to mediate a high demand of protein translation in PTEN-inactive TNBC. Finally, the importance of WDHD1 in TNBC was confirmed in patient samples obtained from the TCGA and tissue microarrays with clinic-pathological information. Taken together, as an essential gene for the survival of PTEN-inactive TNBC cells, WDHD1 could be a potential biomarker or a therapeutic target for TNBC.

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SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity

Cited by 27 publications

References 49 publications

Value of combining PET/CT and clinicopathological features in predicting EGFR mutation in Lung Adenocarcinoma with Bone Metastasis

Value of combining PET/CT and clinicopathological features in predicting EGFR mutation in Lung Adenocarcinoma with Bone Metastasis

Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer

WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer

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