Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer.

By Arkaitz Carracedo, Li Ma, J. Teruya-Feldstein, F. Rojo, L. Salmena, A. Alimonti, Ainara Egia, Atsuo T. Sasaki, G. Thomas, S. Kozma and 5 more. Journal of Clinical Investigation, 2008

1,466 citations recorded by the source corpus.

Subfields: Molecular Biology, Pathology and Forensic Medicine, Pharmacology

View Paper: https://www.semanticscholar.org/paper/1026830b7bd949578f06ef2a22e349920bbaf54f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. J. Engelman
2. P. Pandolfi
3. Arkaitz Carracedo
4. Lewis C. Cantley
5. D. Fruman
6. B. Hopkins
7. R. Abraham
8. Honyin Chiu

In Pathology and Forensic Medicine

1. C. Sawyers
2. P. Pandolfi
3. J. Engelman

In Pharmacology

1. Lewis C. Cantley

Citations in the corpus

• The PI3K pathway in human disease (2017, positive): “…(Figure 2) (Magnuson et al., 2012). mTORC1 also initiates powerful negative feedback regulation of growth factor receptor signaling, such that inhibition of mTORC1 or S6K1 leads to elevated activation of PI3K, AKT, and the ERK pathway (Carracedo et al., 2008; Saxton and Sabatini, 2017).”
• Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. (2011, background): “One potential liability of mTORC1 inhibition is disruption of a negative feedback loop, resulting in hyperactivation of AKT and MAPK that can promote cell survival independent of mTORC1, thereby limiting therapeutic efficacy (Carracedo et al., 2008; O’Reilly et al., 2006; Sarbassov et al., 2005).”
• The mTOR Signalling Pathway in Human Cancer (2012, background): “recruitment and binding to RTKs, leading to a negative feedback regulation of both PI3K [62] and MAPK signalling [63].”
• The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches (2012, background): “These complex interactions are involved in a phenomenon that has been frequently observed following treatment of cancer cells with specific inhibitors directed against the MAPK or the PI3K pathways: the activity of these agents is significantly limited by the fact that blockade of a pathway induces ”
• Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer (2009, background): “It was recently shown that mTORC1 inhibition led to the activation of MAPK in a PI3K-dependent manner, providing another example of such signalling feedback loops and crosstal”