Inhibition of mycobacterial infection by the tumor suppressor PTEN Journal Article

Authors: Huang, G.; Redelman-Sidi, G.; Rosen, N.; Glickman, M. S.; Jiang, X.
Article Title: Inhibition of mycobacterial infection by the tumor suppressor PTEN
Abstract: The tumor suppressor PTEN is a lipid phosphatase that is frequently mutated in various human cancers. PTEN suppresses tumor cell proliferation, survival, and growth mainly by inhibiting the PI3K-Akt signaling pathway through dephosphorylation of phosphatidylinositol 3,4,5-triphosphate. In addition to it role in tumor suppression, the PTEN-PI3K pathway controls many cellular functions, some of which may be important for cellular resistance to infection. Currently, the intersection between tumorigenic signaling pathways and cellular susceptibility to infection is not well defined. In this study we report that PTEN signaling regulates infection of both noncancerous and cancerous cells by multiple intracellular mycobacterial pathogens and that pharmacological modulation of PTEN signaling can affect mycobacterial infection. We found that PTEN deficiency renders multiple types of cells hyper-susceptible to infection by Mycoplasma and Mycobacterium bovis Bacillus Calmette- Guérin (BCG). The lipid phosphatase activity of PTEN is required for attenuating infection. Furthermore, we found mycobacterial infection activates host cell Akt phosphorylation, and pharmacological inhibition of Akt or PI3K activity reduced levels of intracellular infection. Intriguingly, inhibition of mTOR, one of the downstream components of the Akt signaling and a promising cancer therapeutic target, also lowered intracellular Bacillus Calmette-Guérin levels in mammary epithelial cancer MCF-7cells. These findings demonstrate a critical role of PTEN-regulated pathways in pathogen infection. The relationship of PTEN-PI3K-Akt mTOR status and susceptibility to mycobacterial infection suggests that the interaction of mycobacterial pathogens with cancer cells may be influenced by genetic alterations in the tumor cells. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: signal transduction; protein kinase b; controlled study; human cell; neoplasms; cell proliferation; cytology; enzyme inhibition; phosphatase; cancer cell culture; enzyme activity; hela cells; breast neoplasms; phosphorylation; bladder cancer; phosphatidylinositol 3 kinase; urinary bladder neoplasms; prostatic neoplasms; enzyme phosphorylation; enzyme regulation; tumors; cancer cell; pathogens; mammalian target of rapamycin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; proto-oncogene proteins c-akt; pten phosphohydrolase; mycobacterium bovis; tumor suppressor protein; therapeutic targets; cell strain mcf 7; cell interaction; gene knockdown techniques; host cell; infection sensitivity; mycobacteriosis; tuberculosis; cancer cells; human cancer; tumor suppression; tumor suppressors; enzyme deficiency; tumor cells; mycobacterial; signaling pathways; cells; antibiotics; genetic alterations; bacteriology; phosphatases; infection resistance; phosphatidylinositol 3-kinases; tor serine-threonine kinases; mycobacterial infection; mycoplasma; phosphatidylinositol; phosphatase activity; akt phosphorylation; cellular function; pharmacological inhibition; pigments; mycobacterium bovis bcg; cancerous cells; dephosphorylations; downstream components; host cells; pathogen infection; mycoplasma infections
Journal Title: Journal of Biological Chemistry
Volume: 287
Issue: 27
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2012-06-29
Start Page: 23196
End Page: 23202
Language: English
DOI: 10.1074/jbc.M112.351940
PROVIDER: scopus
PMCID: PMC3391101
PUBMED: 22613768
Notes: --- - "Export Date: 1 August 2012" - "CODEN: JBCHA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Neal Rosen
    404 Rosen
  2. Guochang Huang
    15 Huang
  3. Xuejun Jiang
    100 Jiang
  4. Xiaogang Jiang
    1 Jiang