The LKB1 tumor suppressor differentially affects anchorage independent growth of HPV positive cervical cancer cell lines.
Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in known LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor.
Division of Infectious Diseases, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Hildegard I D
HI
Mack
Karl
K
Munger
D000091162:AMP-Activated Protein Kinase Kinases; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D027383:Papillomaviridae / Q000472:pathogenicity*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
Anoikis; Cervical cancer; Human Papillomaviruses; LKB1 kinase; Peutz-Jeghers syndrome; Tumor suppressor