Signaling interplay between transforming growth factor-β receptor and PI3K/AKT pathways in cancer.
The transforming growth factor (TGF)-β and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways are used in cells to control numerous responses, including proliferation, apoptosis, and migration. TGF-β is known for its cytostatic effects in premalignant states and its pro-oncogenic activity in advanced cancers. The pro-cell survival response exerted by growth-factor-mediated activation of PI3K/AKT has been linked to stimulation of tumor formation. Both TGF-β receptor and PI3K/AKT pathways were initially modeled as linear signaling conduits. Although early studies suggested that these two pathways might counteract each other in balancing cell survival, emerging evidence has uncovered multiple modes of intricate signal integration and obligate collaboration in driving cancer progression. These new insights provide the rationale for exploring their dual targeting in cancer.
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Molecular Cell Biology, Cancer Genomics Centre and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: L.Zhang@lumc.nl.
Long
L
Zhang
Fangfang
F
Zhou
Peter
P
ten Dijke
D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction
D018125:Receptors, Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
AKT; SMA- and MAD-related protein (SMAD) transforming growth factor-β; mammalian target of rapamycin complex; phosphatase and tensin homolog deleted on chromosome 10; phosphoinositide 3-kinase