Grifolin inhibits tumor cells adhesion and migration via suppressing interplay between PGC1α and Fra-1 / LSF- MMP2 / CD44 axes.
Grifolin, a farnesyl phenolic compound isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens, exhibits effective antitumor bioactivity in previous study of our group and other lab. In this study, we observed that grifolin inhibited tumor cells adhesion and migration. Moreover, grifolin reduced reactive oxygen species (ROS) production and caused cellular ATP depletion in high-metastatic tumor cells. PGC1α (Peroxisome proliferator-activated receptor γ, coactivator 1α) encodes a transcriptional co-activator involved in mitochondrial biogenesis and respiration and play a critical role in the maintenance of energy homeostasis. Interestingly, grifolin suppressed the mRNA as well as protein level of PGC1α. We further identified that MMP2 and CD44 expressions were PGC1α inducible. PGC1α can bind with metastatic-associated transcription factors: Fra-1 and LSF and the protein-protein interaction was attenuated by grifolin treatment. Overall, these findings suggest that grifolin decreased ROS generation and intracellular ATP to suppress tumor cell adhesion/migration via impeding the interplay between PGC1α and Fra-1 /LSF-MMP2/CD44 axes. Grifolin may develop as a promising lead compound for antitumor therapies by targeting energy metabolism regulator PGC1α signaling.
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Xiangjian
X
Luo
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Namei
N
Li
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Juanfang
J
Zhong
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Zheqiong
Z
Tan
Department of Medicine, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China.
Ying
Y
Liu
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Xin
X
Dong
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Can
C
Cheng
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Zhijie
Z
Xu
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Hongde
H
Li
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Lifang
L
Yang
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Min
M
Tang
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Xinxian
X
Weng
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Wei
W
Yi
School of Pharmacy, South-Central University For Nationalities, Wuhan, Hubei 430074, China.
Jikai
J
Liu
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China.
Ya
Y
Cao
D000255:Adenosine Triphosphate / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013729:Terpenes / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099169:Fos-Related Antigen 1
D000255:Adenosine Triphosphate; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; D020778:Matrix Metalloproteinase 2; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016760:Proto-Oncogene Proteins c-fos; D017382:Reactive Oxygen Species; D013729:Terpenes; D014157:Transcription Factors; D000099169:Fos-Related Antigen 1; C497483:CD44 protein, human; C501906:TFCP2 protein, human; C058858:grifolin
PGC1α; ROS; adhesion; grifolin; migration