4.7 Article

TIMELESS inhibits breast cancer cell invasion and metastasis by down-regulating the expression of MMP9

Journal

CANCER CELL INTERNATIONAL
Volume 21, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12935-021-01752-y

Keywords

TIMELESS; MMP9; Invasion; Metastasis; Breast cancer

Categories

Funding

  1. National Natural Science Foundation of China [81872263, 81672792]
  2. LiaoNing Revitalization Talents Program

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The study revealed that TIMELESS inhibits the invasion and metastasis of breast cancer cells by suppressing the acetylation of p65, inhibiting NF-κB activation, reducing MMP9 expression, and ultimately preventing the spread of breast cancer cells.
Breast cancer is the first killer leading to female death, and tumor metastasis is one of the important factors leading to the death of patients, but the specific mechanism of breast cancer metastasis is not very clear at present. Our study showed that overexpression of TIMELESS could significantly inhibit the invasion and metastasis of breast cancer cells ZR-75-30 and the assembly of F-actin protein. On the contrary, knockdown of TIMELESS promoted the invasion and metastasis of breast cancer cells. Further study revealed that TIMELESS overexpression decreased the mRNA and protein levels of MMP9. Furthermore, TIMELESS could interact with p65, leading to repress the association of p65 and its acetyltransferase CBP and down-regulating the acetylation level of p65, which inhibited the activation of NF-kappa B signal pathway. In conclusion, our research showed that TIMELESS may repress the invasion and metastasis of breast cancer cells via inhibiting the acetylation of p65, inhibiting the activation of NF-kappa B, thus down-regulating the expression of MMP9, and then inhibiting the invasion and metastasis of breast cancer cells.

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