title: Extracellular Matrix Rigidity-dependent Sphingosine-1-phosphate Secretion Regulates Metastatic Cancer Cell Invasion and Adhesion.
abstract: Dynamic interaction between cancer cells and the surrounding microenvironment is critical for cancer progression via changes in cellular behavior including alteration of secreted molecules. However, the molecular mechanisms underlying the influence exerted by the cancer microenvironment on secretion of molecules during cancer progression remain largely unknown. In this study, we report that secretion of spingsine-1-phosphate (S1P) and its regulator, SphK1 expression is dependent of the substrate rigidity, which is critical for the balance between cancer cell invasion and adhesion. Conditioned media (CM) of MDA-MB-231, an aggressive breast cancer cell obtained from soft substrate (~0.5 kPa) induced chemo-attractive invasion, while CM obtained from stiff substrate (~2.5 kPa) increased cell adhesion instead. We found that the expression of SphK1 is upregulated in the stiff substrate, resulting in an increase in S1P levels in the CM. We also found that upregulation of SphK1 expression in the stiff substrate is dominant in metastatic cancer cells but not in primary cancer cells. These results suggest that alterations in the mechanical environment of the ECM surrounding the tumor cells actively regulate cellular properties such as secretion, which in turn, may contribute to cancer progression.
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Panseon
authors.initials: P
authors.lastname: Ko
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Daehwan
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Eunae
authors.initials: E
authors.lastname: You
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Jangho
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Somi
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
authors.forename: Sangmyung
authors.initials: S
authors.lastname: Rhee
mesh_terms: D001696:Biomechanical Phenomena; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D059016:Tumor Microenvironment; D000099157:Sphingosine Kinase
chemical_list: D017077:Culture Media, Conditioned; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate