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Ras and Rap1: A tale of two GTPases

Seema Shah1, Ethan J Brock1, Kyungmin Ji2

  • 1Program in Cancer Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Seminars in Cancer Biology
|April 6, 2018
PubMed

Insights

Ras oncoproteins are difficult to target directly. This review explores how Rap1, a related protein, promotes cancer progression through ERK signaling, offering alternative therapeutic strategies for tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Ras oncoproteins are crucial in tumor development but challenging to target pharmacologically due to their structure.
  • Alternative strategies like mislocalization or targeting downstream pathways are being investigated to inhibit Ras.
  • Ras GTPases regulate fundamental cellular processes, and related proteins like Rap1 also influence cell growth and survival.

Purpose of the Study:

  • To review the role of activated Rap1 in promoting cancer invasion, migration, and metastasis.
  • To elucidate the mechanisms by which Rap1 influences ERK signaling and other downstream pathways.
  • To highlight Rap1 as a potential therapeutic target in Ras-driven cancers.

Main Methods:

  • Literature review of studies investigating Ras and Rap1 signaling pathways.
  • Analysis of Rap1's role in cell adhesion, integrin function, and ERK activation.
  • Examination of Rap1's contribution to cancer phenotypes like invasion and metastasis.

Main Results:

  • Ras and Rap1 cooperate to activate ERK signaling, a common feature in many malignancies.
  • Activated Rap1 promotes cancer cell invasion, migration, and metastasis through various downstream pathways.
  • Rap1's involvement in cell adhesion and integrin function is critical in diverse cell types.

Conclusions:

  • Activated Rap1 plays a significant role in driving cancer progression and metastasis.
  • Targeting Rap1 or its downstream pathways presents a promising therapeutic avenue for Ras-driven cancers.
  • Understanding Rap1's complex interplay with Ras signaling is key to developing effective cancer treatments.
Keywords:
Cell-adhesionEMTERK/MAPKFTIIntegrinsMetabolismRap1Rap1GapRas

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