Zhenzhen Bai1, Qingqing Wu2, Cong Zhang2, Jing Chen2, Liyu Cao1,2. 1. Department of Pathology, Anhui Medical University, Hefei, China. 2. Department of Pathology, Fuyang Hospital of Anhui Medical University, Fuyang, China.
Abstract
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide and has a high mortality rate. With the development of tumor molecular biology, more and more attention is being paid to the mechanisms of cell pathways in colorectal carcinogenesis, such as the Hippo/Yes-associated protein 1 (YAP1) and Wnt/β-catenin signaling pathways. The abnormal expression of YAP1 and β-catenin have been reported in CRC, and can lead to excessive cell proliferation, and eventually, tumor formation. Secreted frizzled-related protein 2 (SFRP2) levels have been found to be decreased in a variety of cancers, and SFRP2 is an antagonist that binds directly to Wnt signal. At present, the molecular basis of colorectal tumors is still not fully understood. In the present study, we sought to identify the molecular mechanisms underlying YAP1 and SFRP2 in the development of CRC. METHODS: We constructed CRC cell lines that stably overexpressed YAP1 and SFRP2 using lentivirus packaging and cell infection. The levels of expression of the proteins were evaluated by western blot and immunofluorescence assays. Protein complex immunoprecipitation (Co-IP) was used to detect the interaction between YAP1, SFRP2, and β-catenin. The functional roles of YAP1 and SFRP2 in CRC was determined by a Cell Counting Kit-8 (CCK8) proliferation assay and flow cytometric apoptosis assay. RESULTS: The data of the present study showed that the overexpression of SFRP2 promoted the expression of YAP1 and β-catenin protein, and the overexpression of YAP1 promoted the expression of β-catenin protein. YAP1 overexpression promoted cell proliferation, while SFRP2 overexpression inhibited cell proliferation and promoted cell apoptosis. CONCLUSIONS: Our findings showed that the expression of YAP1, SFRP2, and β-catenin is correlated in CRC cells. The Hippo pathway and Wnt pathway interact with each other in the pathogenesis of CRC, and YAP1 and SFRP2 are involved in the formation and development of CRC. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide and has a high mortality rate. With the development of tumor molecular biology, more and more attention is being paid to the mechanisms of cell pathways in colorectal carcinogenesis, such as the Hippo/Yes-associated protein 1 (YAP1) and Wnt/β-catenin signaling pathways. The abnormal expression of YAP1 and β-catenin have been reported in CRC, and can lead to excessive cell proliferation, and eventually, tumor formation. Secreted frizzled-related protein 2 (SFRP2) levels have been found to be decreased in a variety of cancers, and SFRP2 is an antagonist that binds directly to Wnt signal. At present, the molecular basis of colorectal tumors is still not fully understood. In the present study, we sought to identify the molecular mechanisms underlying YAP1 and SFRP2 in the development of CRC. METHODS: We constructed CRC cell lines that stably overexpressed YAP1 and SFRP2 using lentivirus packaging and cell infection. The levels of expression of the proteins were evaluated by western blot and immunofluorescence assays. Protein complex immunoprecipitation (Co-IP) was used to detect the interaction between YAP1, SFRP2, and β-catenin. The functional roles of YAP1 and SFRP2 in CRC was determined by a Cell Counting Kit-8 (CCK8) proliferation assay and flow cytometric apoptosis assay. RESULTS: The data of the present study showed that the overexpression of SFRP2 promoted the expression of YAP1 and β-catenin protein, and the overexpression of YAP1 promoted the expression of β-catenin protein. YAP1 overexpression promoted cell proliferation, while SFRP2 overexpression inhibited cell proliferation and promoted cell apoptosis. CONCLUSIONS: Our findings showed that the expression of YAP1, SFRP2, and β-catenin is correlated in CRC cells. The Hippo pathway and Wnt pathway interact with each other in the pathogenesis of CRC, and YAP1 and SFRP2 are involved in the formation and development of CRC. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
Entities:
Keywords:
Yes-associated protein 1 (YAP1); colorectal cancer (CRC); secreted frizzled-related protein 2 (SFRP2); β-catenin
Authors: Jeroen R Huyghe; Stephanie A Bien; Tabitha A Harrison; Hyun Min Kang; Sai Chen; Stephanie L Schmit; David V Conti; Conghui Qu; Jihyoun Jeon; Christopher K Edlund; Peyton Greenside; Michael Wainberg; Fredrick R Schumacher; Joshua D Smith; David M Levine; Sarah C Nelson; Nasa A Sinnott-Armstrong; Demetrius Albanes; M Henar Alonso; Kristin Anderson; Coral Arnau-Collell; Volker Arndt; Christina Bamia; Barbara L Banbury; John A Baron; Sonja I Berndt; Stéphane Bézieau; D Timothy Bishop; Juergen Boehm; Heiner Boeing; Hermann Brenner; Stefanie Brezina; Stephan Buch; Daniel D Buchanan; Andrea Burnett-Hartman; Katja Butterbach; Bette J Caan; Peter T Campbell; Christopher S Carlson; Sergi Castellví-Bel; Andrew T Chan; Jenny Chang-Claude; Stephen J Chanock; Maria-Dolores Chirlaque; Sang Hee Cho; Charles M Connolly; Amanda J Cross; Katarina Cuk; Keith R Curtis; Albert de la Chapelle; Kimberly F Doheny; David Duggan; Douglas F Easton; Sjoerd G Elias; Faye Elliott; Dallas R English; Edith J M Feskens; Jane C Figueiredo; Rocky Fischer; Liesel M FitzGerald; David Forman; Manish Gala; Steven Gallinger; W James Gauderman; Graham G Giles; Elizabeth Gillanders; Jian Gong; Phyllis J Goodman; William M Grady; John S Grove; Andrea Gsur; Marc J Gunter; Robert W Haile; Jochen Hampe; Heather Hampel; Sophia Harlid; Richard B Hayes; Philipp Hofer; Michael Hoffmeister; John L Hopper; Wan-Ling Hsu; Wen-Yi Huang; Thomas J Hudson; David J Hunter; Gemma Ibañez-Sanz; Gregory E Idos; Roxann Ingersoll; Rebecca D Jackson; Eric J Jacobs; Mark A Jenkins; Amit D Joshi; Corinne E Joshu; Temitope O Keku; Timothy J Key; Hyeong Rok Kim; Emiko Kobayashi; Laurence N Kolonel; Charles Kooperberg; Tilman Kühn; Sébastien Küry; Sun-Seog Kweon; Susanna C Larsson; Cecelia A Laurie; Loic Le Marchand; Suzanne M Leal; Soo Chin Lee; Flavio Lejbkowicz; Mathieu Lemire; Christopher I Li; Li Li; Wolfgang Lieb; Yi Lin; Annika Lindblom; Noralane M Lindor; Hua Ling; Tin L Louie; Satu Männistö; Sanford D Markowitz; Vicente Martín; Giovanna Masala; Caroline E McNeil; Marilena Melas; Roger L Milne; Lorena Moreno; Neil Murphy; Robin Myte; Alessio Naccarati; Polly A Newcomb; Kenneth Offit; Shuji Ogino; N Charlotte Onland-Moret; Barbara Pardini; Patrick S Parfrey; Rachel Pearlman; Vittorio Perduca; Paul D P Pharoah; Mila Pinchev; Elizabeth A Platz; Ross L Prentice; Elizabeth Pugh; Leon Raskin; Gad Rennert; Hedy S Rennert; Elio Riboli; Miguel Rodríguez-Barranco; Jane Romm; Lori C Sakoda; Clemens Schafmayer; Robert E Schoen; Daniela Seminara; Mitul Shah; Tameka Shelford; Min-Ho Shin; Katerina Shulman; Sabina Sieri; Martha L Slattery; Melissa C Southey; Zsofia K Stadler; Christa Stegmaier; Yu-Ru Su; Catherine M Tangen; Stephen N Thibodeau; Duncan C Thomas; Sushma S Thomas; Amanda E Toland; Antonia Trichopoulou; Cornelia M Ulrich; David J Van Den Berg; Franzel J B van Duijnhoven; Bethany Van Guelpen; Henk van Kranen; Joseph Vijai; Kala Visvanathan; Pavel Vodicka; Ludmila Vodickova; Veronika Vymetalkova; Korbinian Weigl; Stephanie J Weinstein; Emily White; Aung Ko Win; C Roland Wolf; Alicja Wolk; Michael O Woods; Anna H Wu; Syed H Zaidi; Brent W Zanke; Qing Zhang; Wei Zheng; Peter C Scacheri; John D Potter; Michael C Bassik; Anshul Kundaje; Graham Casey; Victor Moreno; Goncalo R Abecasis; Deborah A Nickerson; Stephen B Gruber; Li Hsu; Ulrike Peters Journal: Nat Genet Date: 2018-12-03 Impact factor: 41.307