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Downregulated adaptor protein p66 Shc mitigates autophagy process by low nutrient and enhances apoptotic resistance in human lung adenocarcinoma A549 cells
Author(s) -
Zheng Zhichao,
Yang Jie,
Zhao Dan,
Gao Dan,
Yan Xiaojie,
Yao Zhi,
Liu Zhe,
Ma Zhenyi
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12416
Subject(s) - autophagy , microbiology and biotechnology , protein kinase b , sequestosome 1 , anoikis , bag3 , biology , signal transduction , protein kinase a , kinase , chemistry , programmed cell death , apoptosis , biochemistry
Macroautophagy or autophagy is a lysosome‐dependent process in which enzymatic degradation and recycling of cytosolic components occur in stressful contexts. The mechanisms underlying the signaling from starvation to the regulation of autophagy are not fully understood. We previously showed that the Src family member p66 Shc (focal adhesion‐associated 66 kDa isoform of the Src homology and collagen) promotes anoikis and suppresses tumor metastasis via k‐Ras‐dependent control of proliferation and survival. However, the role of p66 Shc in low‐nutrient‐induced autophagy‐related pathways remains elusive. In this work, human lung adenocarcinoma A549 cells were used to further investigate the biological effects of p66 Shc on autophagy and apoptotic resistance. Here, we show that deficiency of p66 Shc mitigates the low‐nutrient‐induced autophagy process in the levels of microtubule‐associated protein 1A light chain protein 3B (LC3B) conversion, in the number of autophagic vacuoles and in p62/sequestosome 1 protein degradation. However, autophagy‐related protein Beclin 1 was not significantly changed during low‐nutrient treatment. Furthermore, we found that prolonged phosphorylation of extracellular signaling‐regulated kinase (Erk)1/2, but not phosphorylation of Akt is significantly sustained when p66 Shc expression is inhibited by shRNA. In addition, cleavage of caspase 7 and poly(ADP‐ribose) polymerase, but not caspase 6 and 9 are retarded with this effect compared to the shRNA control cells. Together, these findings suggest the possibility that p66 Shc plays a pivotal role in coordinately regulating autophagy process and apoptotic resistance in A549 cells under nutrient‐limited conditions.