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TFPI-2 suppresses breast cancer cell proliferation and invasion through regulation of ERK signaling and interaction with actinin-4 and myosin-9.

ABSTRACT: TFPI-2 has been recognized as a potent tumor suppressor gene. Low expression of TFPI-2 results in enhanced growth and metastasis of a variety of human tumors. In the present study, we investigated the mechanism responsible for the tumor suppressive effect of TFPI-2. Overexpression of TFPI-2 decreased phosphorylation of ERK1/2 and the translocation of p-ERK1/2 from cytoplasm into the nucleus, and eventually resulted in a reduced cell proliferation. Immunoprecipitation assays identified myosin-9 and actinin-4 as TFPI-2-interacting proteins. Full-length TFPI-2 was required for binding to actinin-4, whereas the N?+?KD1 regions of TFPI-2 were sufficient to interact with myosin-9. Although overexpression of TFPI-2 or TFPI-2/N?+?KD1 does not affect the expression of actinin-4 and myosin-9, it inhibits the migration and invasion of human breast cancer cells. Our results suggest that TFPI-2 suppresses cancer cell proliferation and invasion partly through the regulation of the ERK1/2 signaling and through interactions with myosin-9 and actinin-4.

SUBMITTER: Wang G

PROVIDER: S-EPMC6158255 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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TFPI-2 suppresses breast cancer cell proliferation and invasion through regulation of ERK signaling and interaction with actinin-4 and myosin-9.

Wang Guangli G Huang Wenhe W Li Wei W Chen Shaoying S Chen Weibin W Zhou Yanchun Y Peng Pei P Gu Wei W

Scientific reports 20180926 1

TFPI-2 has been recognized as a potent tumor suppressor gene. Low expression of TFPI-2 results in enhanced growth and metastasis of a variety of human tumors. In the present study, we investigated the mechanism responsible for the tumor suppressive effect of TFPI-2. Overexpression of TFPI-2 decreased phosphorylation of ERK1/2 and the translocation of p-ERK1/2 from cytoplasm into the nucleus, and eventually resulted in a reduced cell proliferation. Immunoprecipitation assays identified myosin-9 a ...[more]

PMID: 30258071

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TFPI-2 suppresses breast cancer cell proliferation and invasion through regulation of ERK signaling and interaction with actinin-4 and myosin-9.

Publications

TFPI-2 suppresses breast cancer cell proliferation and invasion through regulation of ERK signaling and interaction with actinin-4 and myosin-9.

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