Rho GTPase signaling in cancer progression and dissemination

Abstract

Rho GTPases are a family of small G proteins that regulate a wide array of cellular processes related to their key roles controlling the cytoskeleton. On the other hand, cancer is a multi-step disease caused by the accumulation of genetic mutations and epigenetic alterations, from the initial stages of cancer development when cells in normal tissues undergo transformation, to the acquisition of invasive and metastatic traits, responsible for a large number of cancer related deaths. In this review, we discuss the role of Rho GTPase signalling in cancer in every step of disease progression. Rho GTPases contribute to tumour initiation and progression, by regulating proliferation and apoptosis, but also metabolism, senescence and cell stemness. Rho GTPases play a major role in cell migration, and in the metastatic process. They are also involved in interactions with the tumour microenvironment and regulate inflammation, contributing to cancer progression. After years of intensive research, we highlight the importance of relevant models in the Rho GTPase field, and we reflect on the therapeutic opportunities arising for cancer patients.

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

“…EMT is vital for the progression of bladder cancer tumors because it plays a crucial role in cancer cells spreading and invasion [ 91 ]. Numerous signaling proteins contribute to this cellular differentiation process and Rac1 is one of them [ 92 ]. The targeting of the EGFR-Rac1 axis can permit to reverse EMT [ 93 ].…”

Differential Impact of Membrane-Bound and Soluble Forms of the Prognostic Marker Syndecan-1 on the Invasiveness, Migration, Apoptosis, and Proliferation of Cervical Cancer Cells

“…Different forms of Rho Kinases need to be relocated when they change from inactive cytoplasmatic form to activated plasma membrane form (42,46). The involvement of Rho kinases in changes of cell-cell adhesion (42,46) and the participation of Sdc-1 in the formation of focal adhesions is well known (9). Some caveats are associated with the present study.…”

“…Since Sdc-1 and Rho-Kinases regulate cell motility, we suggest soluble Sdc-1 placing Rho B into a different activated status, affecting a change of localization to cell-cell borders. Different forms of Rho Kinases need to be relocated when they change from inactive cytoplasmatic form to activated plasma membrane form (42,46). The involvement of Rho kinases in changes of cell-cell adhesion (42,46) and the participation of Sdc-1 in the formation of focal adhesions is well known (9).…”

Is Cryptosporidium a hijacker able to drive cancer cell proliferation?

“…They are also considered as key players controlling the dynamics of actin-based processes in the formation of lamellipodia, membrane ruffling, and filopodia ( Martin et al, 2002 ). Thus, the Rho GTPase signaling can contribute to the hallmarks of cancer ( Crosas-Molist et al, 2022 ). Interestingly, the signaling cascades activated at the interface between Cryptosporidium and the host are likely similar to these pathways found in the formation of lamellipodia/filopodia ( Lendner and Daugschies, 2014 ).…”