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AC1MMYR2 impairs high dose paclitaxel-induced tumor metastasis by targeting miR-21/CDK5 axis

Yu Ren1, Xuan Zhou2, Juan-Juan Yang3

  • 1Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China.

Cancer Letters
|April 2, 2015
PubMed

Insights

Combining AC1MMYR2 with paclitaxel (taxol) inhibits cancer metastasis. This combination therapy targets the miR-21/CDK5 axis, reducing tumor invasion and spread, offering a promising strategy for improving taxol treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Paclitaxel (taxol) is a key chemotherapy drug for solid tumors.
  • Continuous taxol treatment can paradoxically promote tumor metastasis.
  • The miR-21/CDK5 axis is implicated in cancer progression and metastasis.

Purpose of the Study:

  • To investigate the efficacy of combining AC1MMYR2, a miR-21 inhibitor, with taxol.
  • To determine if this combination can limit taxol-induced tumor metastasis.
  • To elucidate the underlying molecular mechanisms.

Main Methods:

  • In vitro studies using MDA-MB-231 (breast cancer) and U87VIII (glioblastoma) cell lines.
  • Assessing the impact of AC1MMYR2 on the miR-21/CDK5 axis, including CDK5 activity and downstream targets.
  • Evaluating tumor cell migration, invasion, invadopodia formation, and epithelial-mesenchymal transition (EMT) markers.
  • In vivo studies in mice to assess lung metastasis reduction.

Main Results:

  • Abnormal miR-21/CDK5 axis activation correlates with breast cancer lymph node metastasis and taxol-induced invasion/EMT.
  • AC1MMYR2 inhibits CDK5 activity by targeting CDK5RAP1, p39, and p-FAK(ser732).
  • Combination therapy suppressed tumor cell migration and invasion, reduced invadopodia, and reversed EMT markers.
  • Significant reduction in lung metastasis was observed in mice treated with AC1MMYR2 plus taxol.

Conclusions:

  • AC1MMYR2 effectively targets the miR-21/CDK5 axis, counteracting taxol-induced cancer metastasis.
  • The combination therapy demonstrates potential in preventing tumor dissemination.
  • This strategy offers a promising approach for enhancing clinical taxol applications and managing cancer metastasis.
Keywords:
AC1MMYR2CDK5CDK5RAP1MetastasisTaxol

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