title: SIX1 coordinates with TGFβ signals to induce epithelial-mesenchymal transition in cervical cancer.
abstract: Epithelial-mesenchymal transition (EMT) plays a critical role in promoting tumor invasion and metastasis. However, the key cofactors that modulate the signal transduction to induce EMT have note been fully explored to date. The present study reports that sine oculis homeobox homolog 1 (SIX1) is able to promote EMT of cervical cancer by coordinating with transforming growth factor (TGF)β-SMAD signals. The expression of SIX1 was negatively correlated with the expression of the epithelial marker E-cadherin in two independent groups of cervical cancer specimens. SIX1 could promote the transition of mesenchymal phenotype in the presence of active TGFβ signalsin vitroandin vivo. TGFβ-SMAD signals were required for the SIX1-mediated promotion of EMT and metastatic capacity of cervical cancer cells. Together, SIX1 and TGFβ cooperated to induce more remarkable changes in the transition of phenotype than each of them alone, and coordinated to promote cell motility and tumor metastasis in cervical cancer. These results suggest that the coordination of SIX1 and TGFβ signals may be crucial in the EMT program, and that SIX1/TGFβ may be considered a valuable marker for evaluating the metastatic potential of cervical cancer cells, or a therapeutic target in the treatment of cervical cancer.
authors.affiliation: Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Sun
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Yun-Te
authors.initials: YT
authors.lastname: Deng
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
authors.forename: Xiao-Xue
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
authors.forename: Dong-Yi
authors.initials: DY
authors.lastname: Wan
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
authors.forename: Bi-Xin
authors.initials: BX
authors.lastname: Xi
authors.affiliation: Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
authors.forename: Meng-Chen
authors.initials: MC
authors.lastname: Li
authors.affiliation: Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
authors.affiliation: Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Medical Records Room, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shu
authors.affiliation: Department of Medical Records Room, Hubei Cancer Hospital, Wuhan, Hubei 430023, P.R. China.
authors.forename: Ke-Zhi
authors.initials: KZ
authors.lastname: Wu
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Gao
keywords: EMT; SIX1; TGFβ; cervical cancer; metastasis