Method for controlling cancer metastasis or cancer cell migration by modulating the cellular level of lysyl tRNA synthetase
The present invention relates to a novel function of lysyl tRNA synthetase (KRS) which enhances tumor cell migration and affects cancer metastasis via KRS's interaction with laminin receptor (67LR) by its translocation to membrane. More particularly, the present invention relates to a method for modulating cancer metastasis or migration, which comprises regulating intracellular levels of KRS; a composition for preventing or treating cancer; use of expression vector for inhibiting the expression of KRS; a method for preventing or treating cancer; use of an agent for inhibiting an activity of KRS; a method for screening an agent which modulates cancer metastasis or migration; and a method for screening an agent which inhibits the interaction of KRS with 67LR, by said novel function. Thus, KRS can modulate cancer metastasis or migration and furthermore, can modulate intracellular metabolism related to 67LR. The interaction between KRS and 67LR can be used effectively in treating, preventing and/or diagnosing of various diseases or disorders related to the interaction.
1. A method for inhibiting cancer metastasis, comprising:
(a) reducing an intracellular level of lysyl tRNA synthetase (KRS); and
(b) inhibiting an interaction between intracellular lysyl tRNA synthetase (KRS) and laminin receptor (67LR) with an agent that inhibits intracellular KRS activity or an agent that inhibits an interaction between intracellular KRS and 67LR, wherein the inhibited interaction between intracellular KRS and 67LR inhibits cancer metastasis,
wherein the agent is selected from the group consisting of an antisense RNA against a polynucleotide encoding KRS, a siRNA against a polynucleotide encoding KRS, and an antibody against KRS.
2. The method of claim 1 , wherein the lysyl tRNA synthetase (KRS) consists of the amino acid sequence represented by SEQ ID NO: 1.
3. A method for inhibiting cancer cell migration, comprising:
(a) reducing an intracellular level of lysyl tRNA synthetase (KRS); and
(b) inhibiting an interaction between intracellular lysyl tRNA synthetase (KRS) and laminin receptor (67LR) with an agent that inhibits intracellular KRS activity or an agent that inhibits an interaction between intracellular KRS and 67LR, wherein the inhibited interaction between intracellular KRS and 67LR inhibits cancer cell migration,
wherein the agent is selected from the group consisting of an antisense RNA against a polynucleotide encoding KRS, a siRNA against a polynucleotide encoding KRS, and an antibody against KRS.
4. The method of claim 1 , wherein the lysyl tRNA synthetase (KRS) consists of the amino acid sequence represented by SEQ ID NO: 1.