Polypyrimidine tract-binding protein 1-mediated down-regulation of ATG10 facilitates metastasis of colorectal cancer cells.
Autophagy plays complex roles in tumor initiation and development, and the expression of autophagy-related genes (ATGs) is differentially regulated in various cancer cells, depending on their environment. In this study, we analyzed the expressional relationship between polypyrimidine tract-binding protein 1 (PTBP1) and ATG10 in metastatic colorectal cancer. PTBP1 is associated with tumor metastasis in primary colorectal tumors and colorectal cancer liver metastasis (CLM) tissues. In addition, PTPB1 directly interacts with mRNA of ATG10, and regulates ATG10 expression level in colorectal cancer cells. Ectopic expression of PTBP1 decreased ATG10 expression, whereas down-regulation of PTBP1 increased ATG10 level. In contrast to PTBP1, expression of ATG10 was decreased in CLM tissues. Knock down of ATG10 promoted cell migration and invasion of colorectal cancer cells. Moreover, depletion of ATG10 modulated epithelial-mesenchymal transition-associated proteins in colorectal cancer cells: N-cadherin, TCF-8/ZEB1, and CD44 were up-regulated, whereas E-cadherin was down-regulated. Taken together, our findings suggest that expression of ATG10 negatively regulated by PTBP1 is associated with metastasis of colorectal cancer cells.
Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Yoon Kyung
YK
Jo
Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
Seon Ae
SA
Roh
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Heejin
H
Lee
Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Na Yeon
NY
Park
Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Eun Sun
ES
Choi
Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
Ju-Hee
JH
Oh
Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
So Jung
SJ
Park
Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Ji Hyun
JH
Shin
Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
Young-Ah
YA
Suh
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Eun Kyung
EK
Lee
Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea. Electronic address: dhcho@khu.ac.kr.
Dong-Hyung
DH
Cho
Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea; Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: jckim@amc.seoul.kr.
Jin Cheon
JC
Kim
D015703:Antigens, CD / Q000378:metabolism; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism
D015703:Antigens, CD; D000071183:Autophagy-Related Proteins; C497483:CD44 protein, human; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D018960:Hyaluronan Receptors; C450006:PTBP1 protein, human; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D038941:Polypyrimidine Tract-Binding Protein; C581901:ATG10 protein, human
ATG10; Autophagy; EMT; Metastasis; PTBP1