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Comment
. 2020 Feb;10(2):182-184.
doi: 10.1158/2159-8290.CD-19-1327.

A New Rho(d) Map to Diffuse Gastric Cancer

Dorothy Benton  1 , Jonathan Chernoff  2
Affiliations
Comment

A New Rho(d) Map to Diffuse Gastric Cancer

Dorothy Benton et al. Cancer Discov. 2020 Feb.

Abstract

Diffuse gastric cancer (DGC) is characterized by frequent missense mutations in the small GTPase RHOA, but the effects of this mutation on enzyme activity and signaling have been widely debated. In this issue, Zhang and colleagues show that the most common RHOA mutation in DGC, encoding RHOAY42C, represents a gain of function; that a mouse model incorporating this mutation in association with loss of the E-cadherin gene CDH1 recapitulates many aspects of DGC; and that rationally designed therapeutics based on our understanding of RHOA signaling are promising agents for treating DGC.See related article by Zhang et al., p. 288.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest:

No potential conflicts of interest were disclosed.

Figures

Figure 1.
Figure 1.. Model for RhoA signaling in DGC.
A) Signaling pathways evoked by RhoAY42C and their contributions to transformation. B) Destabilization of RhoA by Tyr 42 phosphorylation. Wild-type RhoA cycles between GDP and GTP bound states. Met phosphorylates RhoA on Tyr42, promoting subsequent ubiquitination and subsequent destruction. The Y42C mutant exhibits impaired intrinsic and GAP-mediated GTP hydrolysis and cannot be phosphorylated by Met, potentially stabilizing RhoA.
See this image and copyright information in PMC

Comment on

References

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