TY - JOUR
T1 - TNNC1 knockout reverses metastatic potential of ovarian cancer cells by inactivating epithelial-mesenchymal transition and suppressing F-actin polymerization
AU - Yin, Jing Hu
AU - Elumalai, Perumal
AU - Kim, So Youn
AU - Zhang, Song Zi
AU - Shin, Sun
AU - Lee, Minho
AU - Chung, Yeun Jun
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/4/2
Y1 - 2021/4/2
N2 - Troponin C type 1 (TNNC1) is commonly overexpressed in ovarian cancer. However, the biological implications of TNNC1 overexpression on ovarian cancer malignization and its related mechanism remain unknown. To elucidate these implications, we knocked out the TNNC1 gene in TNNC1-overexpressing SKOV-3-13 ovarian cancer cells using CRISPR/Cas-9 technology and observed the changes in metastatic phenotypes and related molecular pathways. TNNC1-knockout (KO) cells showed significantly reduced proliferation and colony formation when compared with TNNC1 wild-type cells (P < 0.01). In TNNC1-KO cells, wound healing, migration, and invasive phenotypes decreased. Upon observation of upstream regulators of epithelial-mesenchymal transition (EMT), levels of phosphorylated AKT (Ser-473 and Thr-308) and GSK-3β (inactive form) were found to be decreased in TNNC1-KO cells. Accordingly, SNAIL and SLUG expression decreased and were almost completely localized in the cytoplasm following TNNC1 silencing. Regarding downstream EMT markers, N-cadherin and vimentin expression decreased, but E-cadherin expression increased. Related matrix metalloproteinase and chemokine expression generally decreased. TNNC1 deficiency also suppressed F-actin polymerization. In conclusion, TNNC1 overexpression contributes to the metastatic behavior of ovarian cancer by perturbation of EMT and actin microfilaments. Our results provide a better understanding of the detailed molecular mechanism of ovarian cancer metastasis associated with TNNC1 overexpression.
AB - Troponin C type 1 (TNNC1) is commonly overexpressed in ovarian cancer. However, the biological implications of TNNC1 overexpression on ovarian cancer malignization and its related mechanism remain unknown. To elucidate these implications, we knocked out the TNNC1 gene in TNNC1-overexpressing SKOV-3-13 ovarian cancer cells using CRISPR/Cas-9 technology and observed the changes in metastatic phenotypes and related molecular pathways. TNNC1-knockout (KO) cells showed significantly reduced proliferation and colony formation when compared with TNNC1 wild-type cells (P < 0.01). In TNNC1-KO cells, wound healing, migration, and invasive phenotypes decreased. Upon observation of upstream regulators of epithelial-mesenchymal transition (EMT), levels of phosphorylated AKT (Ser-473 and Thr-308) and GSK-3β (inactive form) were found to be decreased in TNNC1-KO cells. Accordingly, SNAIL and SLUG expression decreased and were almost completely localized in the cytoplasm following TNNC1 silencing. Regarding downstream EMT markers, N-cadherin and vimentin expression decreased, but E-cadherin expression increased. Related matrix metalloproteinase and chemokine expression generally decreased. TNNC1 deficiency also suppressed F-actin polymerization. In conclusion, TNNC1 overexpression contributes to the metastatic behavior of ovarian cancer by perturbation of EMT and actin microfilaments. Our results provide a better understanding of the detailed molecular mechanism of ovarian cancer metastasis associated with TNNC1 overexpression.
KW - AKT/GSK-3β/SNAIL signaling
KW - Epithelial-mesenchymal transition (EMT)
KW - Ovarian cancer
KW - Troponin C type 1 (TNNC1)
UR - http://www.scopus.com/inward/record.url?scp=85100605251&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2021.02.021
DO - 10.1016/j.bbrc.2021.02.021
M3 - Article
C2 - 33592378
AN - SCOPUS:85100605251
SN - 0006-291X
VL - 547
SP - 44
EP - 51
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -
