title: c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.
abstract: Aberrant expression of c-Ski oncoprotein in some tumor cells has been shown to be associated with cancer development. However, the role of c-Ski in cancer-associated fibroblasts (CAFs) of tumor microenvironment has not been characterized. In the current study, we found that c-Ski is highly expressed in CAFs derived from breast carcinoma microenvironment and this CAF-associated c-Ski expression is associated with invasion and metastasis of human breast tumors. We showed that c-Ski overexpression in immortalized breast normal fibroblasts (NFs) induces conversion to breast CAFs by repressing p53 and thereby upregulating SDF-1 in NFs. SDF-1 treatment or p53 knockdown in NFs had similar effects on the activation of NFs as c-Ski overexpression. The c-Ski-activated CAFs show increased proliferation, migration, invasion and contraction compared with NFs. Furthermore, c-Ski-activated CAFs facilitated the migration and invasion of MDA-MB-231 breast cancer cells. Our data suggest that c-Ski is an important regulator in the activation of CAFs and may serve as a potential therapeutic target to block breast cancer progression.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.|Experimental teaching center of Basic Medicine Science, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Liuyang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zongyue
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Endocrine and Breast Surgery, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Guanglun
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Surgery, Department of Obstetrics and Gynecology, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center. Los Angeles, CA 91006, USA.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Manran
authors.initials: M
authors.lastname: Liu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C060614:SKI protein, human
keywords: CAFs; P53; SDF-1; Tumor microenvironment; c-Ski