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RLIP inhibition suppresses breast-to-lung metastasis

Jyotsana Singhal1, Shireen Chikara2, David Horne3

  • 1Department of Medical Oncology, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA; Department of Molecular Medicine, City of Hope Comprehensive Cancer Center and National Medical Center, Duarte, CA, 91010, USA.

Cancer Letters
|January 27, 2019
PubMed

Insights

This study shows that 2'-hydroxyflavanone (2HF) combined with RLIP inhibition effectively suppresses breast tumor growth and lung metastasis. This combination therapy offers a promising strategy for treating aggressive breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Breast cancer metastasis, particularly to the lungs, is a major cause of cancer mortality.
  • Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and limited treatment options.
  • RLIP (Ras and␮-associated protein 1) is implicated in cancer cell proliferation and metastasis.

Purpose of the Study:

  • To investigate the anti-proliferative and anti-metastatic effects of 2 -hydroxyflavanone (2HF) and RLIP inhibition in triple-negative breast cancer (TNBC).
  • To evaluate the efficacy of combining 2HF with RLIP inhibition strategies (antisense oligonucleotide and antibody) in preclinical models.

Main Methods:

  • In vitro studies using TNBC cell lines to assess cell viability, migration, and invasion.
  • In vivo orthotopic mouse model of breast-to-lung metastasis using luciferase-expressing TNBC cells.
  • Treatment groups included 2HF, RLIP antisense (RAS), RLIP antibody (Rab), and combination therapies.

Main Results:

  • RLIP inhibition alone reduced in vitro cell viability, migration, and invasion.
  • 2HF treatment decreased the expression of RLIP, KRAS, pERK, pSTAT3, and pP70S6K in vitro.
  • Combined treatment with 2HF, RAS, and Rab significantly reduced primary tumor weight and completely abolished lung metastasis in mice, outperforming single-agent therapies.

Conclusions:

  • 2 -hydroxyflavanone (2HF) demonstrates significant anti-proliferative and anti-metastatic properties in TNBC models.
  • RLIP inhibition, via antisense or antibody, is effective in suppressing breast cancer progression and metastasis.
  • The combination of 2HF with RLIP inhibition presents a potent therapeutic strategy for overcoming breast tumor growth and lung metastasis.
Keywords:
Breast cancerChemotherapeuticsLungMetastasisPhytochemicalsRLIP

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