Rho GTPases modulate malignant transformation of tumor cells

Abstract

Rho GTPases are involved in the acquisition of all the hallmarks of cancer, which comprise 6 biological capabilities acquired during the development of human tumors. The hallmarks include proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis programs, as defined by Hanahan and Weinberg. (1) Controlling these hallmarks are genome instability and inflammation. Emerging hallmarks are reprogramming of energy metabolism and evading immune destruction. To give a different view to the readers, we will not be focusing on invasion, metastasis, or cytoskeletal remodeling, but we will review here how Rho GTPases contribute to other hallmarks of cancer with a special emphasis on malignant transformation.

Keywords: Rho GTPases; inflammation; metabolism; oncogene; proliferation; senescence; survival; transformation; tumor progression.

Figure 1. Roles of Rho GTPases during malignant transformation and tumor progression. Diagram showing different roles of Rho GTPases during cell transformation and tumor progression. Upon cell transformation, Rho GTPases contribute—alone or in cooperation with oncogenes—to aberrant proliferation, altered metabolism, increased survival, and evasion of senescence and apoptosis, which will sustain tumor proliferation. Later on, Rho GTPases also contribute to the development of an inflammatory environment, which increases cell survival and tumor progression; and to the induction of tumor angiogenesis, which will sustain tumor growth further and may also serve as an escape route for cancer cells to colonize distant organs. Rho GTPases are also essential for the cytoskeletal changes underlying cell motility and invasion, which allow cancer cells to migrate away from the primary tumor and invade surrounding and later distant tissues, ultimately developing metastasis.