Regulation and functions of RhoU and RhoV

Hodge, Richard G.; Ridley, Anne J.

doi:10.1080/21541248.2017.1362495

Cited by 40 publications

(34 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We thus began to consider whether post-translational modification of RhoU was impaired. RhoU is thought to be targeted to membranes by palmitoylation [16] and we confirmed that RhoU can be palmitoylated (Fig. 3b).…”

Section: Fasn Depletion Reduces Rhou Palmitoylationsupporting

confidence: 79%

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

et al. 2020

View full text Add to dashboard Cite

Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.

show abstract

Section: Fasn Depletion Reduces Rhou Palmitoylationsupporting

confidence: 79%

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

et al. 2020

View full text Add to dashboard Cite

show abstract

“…ZCL278 blocks the interaction of Cdc42 with intersectin (Friesland et al, 2013) and can inhibit the growth of lung cancer xenografts (Aguilar et al, 2019). It is important to note that the activity of atypical Rho GTPases is unlikely to be regulated by GEF/GAP interactions (Aspenstrom et al, 2007;Hodge and Ridley, 2017), and therefore alternative strategies will be required to target these family members effectively.…”

Section: Targeting Rho Gtpase Activationmentioning

confidence: 99%

Targeting Rho GTPase Signaling Networks in Cancer

Clayton

Ridley

2020

Front. Cell Dev. Biol.

Self Cite

139

View full text Add to dashboard Cite

As key regulators of cytoskeletal dynamics, Rho GTPases coordinate a wide range of cellular processes, including cell polarity, cell migration, and cell cycle progression. The adoption of a pro-migratory phenotype enables cancer cells to invade the stroma surrounding the primary tumor and move toward and enter blood or lymphatic vessels. Targeting these early events could reduce the progression to metastatic disease, the leading cause of cancer-related deaths. Rho GTPases play a key role in the formation of dynamic actin-rich membrane protrusions and the turnover of cell-cell and cellextracellular matrix adhesions required for efficient cancer cell invasion. Here, we discuss the roles of Rho GTPases in cancer, their validation as therapeutic targets and the challenges of developing clinically viable Rho GTPase inhibitors. We review other therapeutic targets in the wider Rho GTPase signaling network and focus on the four best characterized effector families: p21-activated kinases (PAKs), Rho-associated protein kinases (ROCKs), atypical protein kinase Cs (aPKCs), and myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs).

show abstract

“…The RhoU/RhoV and RhoD/RhoF subfamilies represent another type of atypical Rho GTPases. These family members have high intrinsic guanine nucleotide exchange activity, and are assumed to be mostly GTP-bound in cells [17,18]. Because these atypical Rho GTPases also have GTPase activity and can cycle between GDP-bound and GTP-bound forms, they are considered to be the fast-cycling Rho GTPases [6,19,20].…”

Section: Regulation Of Rho Gtpases By Ptmsmentioning

confidence: 99%

Dysregulation of Rho GTPases in Human Cancers

Jung

Yoon

Lim

et al. 2020

Cancers

View full text Add to dashboard Cite

Rho GTPases play central roles in numerous cellular processes, including cell motility, cell polarity, and cell cycle progression, by regulating actin cytoskeletal dynamics and cell adhesion. Dysregulation of Rho GTPase signaling is observed in a broad range of human cancers, and is associated with cancer development and malignant phenotypes, including metastasis and chemoresistance. Rho GTPase activity is precisely controlled by guanine nucleotide exchange factors, GTPase-activating proteins, and guanine nucleotide dissociation inhibitors. Recent evidence demonstrates that it is also regulated by post-translational modifications, such as phosphorylation, ubiquitination, and sumoylation. Here, we review the current knowledge on the role of Rho GTPases, and the precise mechanisms controlling their activity in the regulation of cancer progression. In addition, we discuss targeting strategies for the development of new drugs to improve cancer therapy.

show abstract

Regulation and functions of RhoU and RhoV

Cited by 40 publications

References 44 publications

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

Targeting Rho GTPase Signaling Networks in Cancer

Dysregulation of Rho GTPases in Human Cancers

Contact Info

Product

Resources

About