α-enolase promotes tumorigenesis and metastasis via regulating AMPK/mTOR pathway in colorectal cancer.

The α-enolase (ENO1) plays pivotal roles in several types of cancer, but its clinical significance, functional role, and possible mechanism in colorectal cancer (CRC) have remained unclear. Expression level of ENO1 in CRC tissues was examined by qRT-PCR, Western blot, and immunohistochemistry. The effects of ENO1 on cell growth were investigated by MTT, colony formation, flow cytometry assays, and in vivo tumorigenic capacity analysis. The impacts of ENO1 on cell migration and invasion were also explored by scratch-healing, Transwell or Matrigel chamber assays, and in vivo metastatic capacity analysis. Our results showed that the expression level of ENO1 was significantly elevated in CRC tissues. High expression level of ENO1 was associated with disease progression in CRC patients. Overexpression of ENO1 in HCT116 cell line promoted cell proliferation, migration, and invasion in vitro as well as tumorigenesis and metastasis in vivo. In other hand, ablation of ENO1 in HCT116 cells led to totally reverse effects. Mechanistically, we revealed ENO1 could regulate AMPK/mTOR signaling pathway. AMPK pathway activation or mTOR pathway suppression blocked these ENO1 induced alterations. Together, our results demonstrated that ENO1 is a potent promoter of CRC genesis and metastasis at least in part though regulating AMPK/mTOR pathway. These findings also suggested that ENO1 may be a promising therapeutic target in CRC patients.

Zhan P ，Zhao S ，Yan H ，Yin C ，Xiao Y ，Wang Y ，Ni R ，Chen W ，Wei G ，Zhang P ... -  《-》

Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis.

Yuan Z ，Hu H ，Zhu Y ，Zhang W ，Fang Q ，Qiao T ，Ma T ，Wang M ，Huang R ，Tang Q ，Gao F ，Zou C ，Gao X ，Wang G ，Wang X ... -  《Cell Death & Disease》

Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway.

Fu QF ，Liu Y ，Fan Y ，Hua SN ，Qu HY ，Dong SW ，Li RL ，Zhao MY ，Zhen Y ，Yu XL ，Chen YY ，Luo RC ，Li R ，Li LB ，Deng XJ ，Fang WY ，Liu Z ，Song X ... -  《Journal of Hematology & Oncology》

Tumor-intrinsic CD47 signal regulates glycolysis and promotes colorectal cancer cell growth and metastasis.

Rationale: CD47 plays a vital role in the immune escape of tumor cells, but its role in regulating immune-unrelated biological processes such as proliferation and metastasis remains unclear. We seek to explore the immune-independent functions of CD47 in colorectal cancer (CRC). Methods: The expression of CD47 in CRC was determined by immunohistochemistry. The biological effect of CD47 signaling on tumor cell proliferation and metastasis was evaluated in vitro and in vivo. RNA sequencing analysis was performed to identify pivotal signaling pathways modulated by CD47. The interaction between CD47 and ENO1 was verified by co-immunoprecipitation (co-IP). The effect of CD47 on glycolytic metabolites was analyzed by seahorse XF and targeted metabolomics. Results: The expression of CD47 was upregulated and correlated to poor prognosis in CRC patients. Functional assays revealed that CD47 promoted CRC cell growth and metastasis in vitro and in vivo. Our mechanistic investigations demonstrated that CD47 interacted with ENO1 and protected it from ubiquitin-mediated degradation, subsequently promoting glycolytic activity and phosphorylation of ERK in CRC cells. Inhibition of ENO1 diminished CD47-mediated cell growth and migration. Clinically, the combined expression of CD47 and ENO1 provided reliable predictive biomarkers for the prognosis of CRC patients. Conclusions: CD47 is overexpressed in CRC, and its expression is associated with poor prognosis. Through stabilizing ENO1, CD47 enhances the aerobic glycolysis and ERK activity in CRC cells, thereby promoting the progression of CRC. Our studies reveal an unconventional role of CD47, suggesting that targeting the CD47-ENO1 axis may provide a novel therapeutic avenue for CRC.

Hu T ，Liu H ，Liang Z ，Wang F ，Zhou C ，Zheng X ，Zhang Y ，Song Y ，Hu J ，He X ，Xiao J ，King RJ ，Wu X ，Lan P ... -  《Theranostics》

Upregulation of α enolase (ENO1) crotonylation in colorectal cancer and its promoting effect on cancer cell metastasis.

Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.

Hou JY ，Cao J ，Gao LJ ，Zhang FP ，Shen J ，Zhou L ，Shi JY ，Feng YL ，Yan Z ，Wang DP ，Cao JM ... -  《-》