JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance

Wang, Tianyi; Fahrmann, Johannes F.; Lee, Heehyoung; Li, Yijia; Tripathi, Satyendra Chandra; Yue, Chanyu; Zhang, Chunyan; Lifshitz, Veronica; Song, Jieun; Yuan, Yuan; Somlo, George; Jandial, Rahul; Ann, David K.; Hanash, Samir M.; Jove, Richard; Yu, Hua

doi:10.1016/j.cmet.2018.04.018

Cited by 116 publications

(75 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanisms of PD-L1 regulation was multifaceted and at highly complex manners 3 , 4 . As is well-known, JAK/STAT3 is a classical signaling pathway which plays a crucial part in the initiation and development of various cancers 24 , 33 . We found that the effects of IL-8 on PD-L1 expression was more remarkable than IL-6 even though they had similar influence on the activation of STAT3.…”

Section: Discussionmentioning

confidence: 99%

Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis

et al. 2018

View full text Add to dashboard Cite

The expression of PD-L1 in tumor cells is one of the main causes of tumor immune escape. However, the exact mechanism for regulating PD-L1 expression in gastric cancer (GC) cells remains unclear. Our previous studies have shown that mesenchymal stem cells (MSCs) exert broad immunosuppressive potential, modulating the activity of cells either in innate or adaptive immune system to promote tumor progress. This study aims to investigate whether GCMSCs regulate the PD-L1 expression in GC cells and explore the specific molecular mechanism. The results have shown that GCMSCs enhanced PD-L1 expression in GC cells resulting in the resistance of GC cells to CD8+ T cells cytotoxicity. However, this resistance was attenuated with IL-8 inhibition. Further studies proved that IL-8 derived from GCMSCs induced PD-L1 expression in GC cells via c-Myc regulated by STAT3 and mTOR signaling pathways. Our data indicated that blocking IL-8 derived from GCMSCs may overcome the immune escape induced by PD-L1 in GC cells and provide a potential strategy to enhance the immunotherapy efficiency in GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…These findings indicate that the FFA level is pathogenically involved in cancer, which was clearly demonstrated in several studies in related fields. Recent advances in proteomics and metabolomics have deepened our understanding of the role of fatty acid metabolism in determining the fate of cancer cells (Li et al 2017;Wang et al 2018;Madak-Erdogan et al 2019). The TG/FFA cycle participate various metabolic, physiological, and signaling pathways in cells.…”

Section: Discussionmentioning

confidence: 99%

A high serum-free fatty acid level is associated with cancer

Zhang

Han

et al. 2019

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Purpose The objectives of this work were to investigate whether the serum-free fatty acid (FFA) level is meaningful in cancer patients and its role in cancer diagnosis. Methods A total of 2206 patients were divided into a cancer group (n = 1019) and a noncancer group (n = 1187). Age, sex, body mass index (BMI), and serum FFA and serum albumin levels were collected. Cancer patients were divided into subgroups according to the location of the cancer. We then compared serum FFA levels among the tumor subgroups. A receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of the FFA level. SPSS 22.0 software was used to analyze the results. Results The FFA level was higher in the cancer group than in the noncancer group. According to the multivariate analysis, there was also an increased risk of cancer associated with a high FFA level after adjusting for old age, female sex, and a low BMI. In the subgroup analysis, the FFA level in patients with lung cancer, gastric cancer, thyroid cancer, rectal cancer, colon cancer, and ovarian cancer was significantly higher than that in noncancer patients. The area under the effect-time curve (AUC) of FFAs in the whole cancer group was 0.58, while the thyroid cancer, rectal cancer, and ovarian cancer subgroups had AUCs > 0.6. Conclusion Our study provides clinical evidence to support that fatty acid metabolism is associated with cancers and demonstrates that a high FFA level in the serum may be an indicator of cancer.

show abstract

“…Maintenance of cellular energy stores by FAO has been shown to be fundamental to the survival of CSCs in scarce nutrient environments [13]. Multiple reports have highlighted the importance of increased exogenous fatty acid metabolism in CSCs [14].…”

Section: Introductionmentioning

confidence: 99%

Lipid Droplets Define a Sub-Population of Breast Cancer Stem Cells

Hershey

Vazzana

Joppi

et al. 2019

JCM

View full text Add to dashboard Cite

Tumor recurrence is now the leading cause of breast cancer-related death. These recurrences are believed to arise from residual cancer stem cells that survive initial therapeutic intervention. Therefore, a comprehensive understanding of cancer stem cell biology is needed to generate more effective therapies. Here we investigate the association between dysregulation of lipid metabolism and breast cancer stem cells. Focusing specifically on lipid droplets, we found that the lipid droplet number correlates with stemness in a panel of breast cell lines. Using a flow cytometry-based method developed for this study, we establish a means to isolate cells with augmented lipid droplet loads from total populations and show that they are enriched in cancer stem cells. Furthermore, pharmacological targeting of fatty acid metabolism reveals a metabolic addiction in a subset of cell lines. Our results highlight a key role for the lipid metabolism in the maintenance of the breast cancer stem cell pool, and as such, suggest it as a potential therapeutic target.

show abstract

JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance

Cited by 116 publications

References 1 publication

Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis

Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis

A high serum-free fatty acid level is associated with cancer

Lipid Droplets Define a Sub-Population of Breast Cancer Stem Cells

Contact Info

Product

Resources

About