Abstract
Stress granules (SG) are cytoplasmic RNA granules that form during various types of stress known to inhibit general translation, including oxidative stress, hypoxia, endoplasmic reticulum stress (ER), ionizing radiations or viral infection. Induction of these SG promotes cell survival in part through sequestration of proapoptotic molecules, resulting in the inactivation of cell death pathways. SG also form in cancer cells, but studies investigating their formation upon treatment with chemotherapeutics are very limited. Here we identified Lapatinib (Tykerb / Tyverb®), a tyrosine kinase inhibitor used for the treatment of breast cancers as a new inducer of SG in breast cancer cells. Lapatinib-induced SG formation correlates with the inhibition of general translation initiation which involves the phosphorylation of the translation initiation factor eIF2α through the kinase PERK. Disrupting PERK-SG formation by PERK depletion experiments sensitizes resistant breast cancer cells to Lapatinib. This study further supports the assumption that treatment with anticancer drugs activates the SG pathway, which may constitute an intrinsic stress response used by cancer cells to resist treatment.
Highlights
Stress granules are RNA cytoplasmic foci that emerge as a result of accumulation of either untranslated mRNAs or deficient translation initiation complexes [1,2,3] when general translation initiation is blocked
N6-methyladenosine (m6A) is a specific methylation that occurs at specific adenosine residues in a large variety of mRNAs [26]. m6A antibodies have been recently used in immunofluorescence experiments, detecting methylated RNA into Stress granules (SG) induced by arsenite treatment [27]
No SG formation was observed in MDA-MB-231 or Hs578T breast cancer cell lines (S1 Data), indicating that SG formation induced by Lap in breast cancer is cell-type specific
Summary
Stress granules ( referred as cytoplasmic phase transition or droplets) are RNA cytoplasmic foci that emerge as a result of accumulation of either untranslated mRNAs or deficient translation initiation complexes [1,2,3] when general translation initiation is blocked. This occurs during various translational stresses known to inhibit general translation including treatment with genotoxic drugs inducers of oxidative and ER stress, exposure to hypoxia, and treatment with either heat shock or radiation [4,5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
