The cross-talk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer

Jin, Zhijian; Lu, Yifan; Xin, Wu; Pan, Tao; Zhou, Yu; Hou, Junyi; Wu, Airong; Li, Jianfang; Yang, Zhongyi; Li, Chen; Yan, Min; Yan, Chao; Zhu, Zhenggang; Liu, Bingya; Qiu, Weihua; Su, Liping

doi:10.1016/j.redox.2021.102076

Cited by 63 publications

(40 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neurotrophins and their receptors have been regarded as potential therapeutic targets in breast cancer [218][219][220]. On the other hand, neurotrophins are also released by CAFs and exert their biological functions in various types of cancer [221,222] including breast cancer [223]. Thus, a reasonable assumption is that CAFs affect the malignancy of breast cancer cells by releasing neurotrophins, although this mechanism has rarely been reported in breast cancer studies.…”

Section: Other Proteinsmentioning

confidence: 99%

Cancer‐associated fibroblasts in breast cancer: Challenges and opportunities

Zheng

et al. 2022

Cancer Communications

109

View full text Add to dashboard Cite

show abstract

Section: Other Proteinsmentioning

confidence: 99%

Cancer‐associated fibroblasts in breast cancer: Challenges and opportunities

Zheng

et al. 2022

Cancer Communications

109

View full text Add to dashboard Cite

show abstract

“…Finally, BDNF released from CAFs promotes therapy resistance via the TrkB/Keap1-Nrf2 pathway. Cancer cell-derived lactate upregulates BDNF expression in CAFs via the NF-κB pathway, thereby promoting a feedback amplification loop ( 98 ).…”

Section: Evs From Cafs In Cancer Therapy Resistancementioning

confidence: 99%

Role of the Pro-Inflammatory Tumor Microenvironment in Extracellular Vesicle-Mediated Transfer of Therapy Resistance

et al. 2022

View full text Add to dashboard Cite

Advances in our understanding of cancer biology have contributed to generating different treatments to improve the survival of cancer patients. However, although initially most of the therapies are effective, relapse and recurrence occur in a large percentage of these cases after the treatment, and patients then die subsequently due to the development of therapy resistance in residual cancer cells. A large spectrum of molecular and cellular mechanisms have been identified as important contributors to therapy resistance, and more recently the inflammatory tumor microenvironment (TME) has been ascribed an important function as a source of signals generated by the TME that modulate cellular processes in the tumor cells, such as to favor the acquisition of therapy resistance. Currently, extracellular vesicles (EVs) are considered one of the main means of communication between cells of the TME and have emerged as crucial modulators of cancer drug resistance. Important in this context is, also, the inflammatory TME that can be caused by several conditions, including hypoxia and following chemotherapy, among others. These inflammatory conditions modulate the release and composition of EVs within the TME, which in turn alters the responses of the tumor cells to cancer therapies. The TME has been ascribed an important function as a source of signals that modulate cellular processes in the tumor cells, such as to favor the acquisition of therapy resistance. Although generally the main cellular components considered to participate in generating a pro-inflammatory TME are from the immune system (for instance, macrophages), more recently other types of cells of the TME have also been shown to participate in this process, including adipocytes, cancer-associated fibroblasts, endothelial cells, cancer stem cells, as well as the tumor cells. In this review, we focus on summarizing available information relating to the impact of a pro-inflammatory tumor microenvironment on the release of EVs derived from both cancer cells and cells of the TME, and how these EVs contribute to resistance to cancer therapies.

show abstract

“…Besides, lactate produced by aerobic glycolysis can be secreted into the extracellular environment as a signaling molecule to regulate intercellular interactions ( Liao et al, 2021 ). In gastric cancer, lactate derived from tumor cells mediates the up-regulation of BDNF expression in cancer-associated fibroblasts by activating the NF-κB pathway, eventually resulting in acquired resistance ( Jin et al, 2021 ). Alterations in lactate metabolism have been shown to be associated with cell invasion, migration, angiogenesis, drug resistance, and immune escape.…”

Section: Introductionmentioning

confidence: 99%

A Novel Lactate Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironment in Hepatocellular Carcinoma

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the main subtype of primary liver cancer with high malignancy and poor prognosis. Metabolic reprogramming is a hallmark of cancer and has great importance on the tumor microenvironment (TME). As an abundant metabolite, lactate plays a crucial role in cancer progression and the immunosuppressive TME. Nonetheless, the potential roles of lactate in HCC remain unclear. In this study, we downloaded transcriptomic data of HCC patients with corresponding clinical information from the TCGA and ICGC portals. The TCGA-HCC dataset used as the training cohort, while the ICGC-LIRI-JP dataset was served as an external validation cohort. Cox regression analysis and the LASSO regression model were combined to construct the lactate metabolism-related gene signature (LMRGS). Then, we assessed the clinical significance of LMRGS in HCC. Besides, enriched molecular functions, tumor mutation burden (TMB), infiltrating immune cells, and immune checkpoint were comprehensively analyzed in different LMRGS subgroups. In total, 66 differentially expressed lactate metabolism-related genes (LMRGs) were screened. The functions of LMRGs were mainly enriched in mitochondrial activity and metabolic processes. The LMRGS comprised of six key LMRGs (FKTN, PDSS1, PET117, PUS1, RARS1, and RNASEH1) had significant clinical value for independently predicting the prognosis of HCC patients. The overall survival and median survival of patients in the LMRGS-high group were significantly shorter than in the LMRGS-low group. In addition, there were differences in TMB between the two LMRGS subgroups. The probability of genetic mutations was higher in the LMRGS-high group. Most importantly, the LMRGS reflected the TME characteristics. In the LMRGS-high group, the immune microenvironment presented a suppressed state, accompanied by more inhibitory immune cell infiltration, including follicular helper T cells and regulatory T cells. Additionally, the expression of inhibitory checkpoint molecules was much higher in the LMRGS-high group. Our study suggested that the LMRGS was a robust biomarker to predict the clinical outcomes and evaluate the TME of patients with HCC.

show abstract

The cross-talk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer

Cited by 63 publications

References 54 publications

Cancer‐associated fibroblasts in breast cancer: Challenges and opportunities

Cancer‐associated fibroblasts in breast cancer: Challenges and opportunities

Role of the Pro-Inflammatory Tumor Microenvironment in Extracellular Vesicle-Mediated Transfer of Therapy Resistance

A Novel Lactate Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironment in Hepatocellular Carcinoma

Contact Info

Product

Resources

About