000120985 001__ 120985
000120985 005__ 20240731103313.0
000120985 0247_ $$2doi$$a10.1038/s41388-022-02563-9
000120985 0248_ $$2sideral$$a131439
000120985 037__ $$aART-2023-131439
000120985 041__ $$aeng
000120985 100__ $$aClavaín, L.
000120985 245__ $$aCharacterization of mutant versions of the R-RAS2/TC21 GTPase found in tumors
000120985 260__ $$c2023
000120985 5060_ $$aAccess copy available to the general public$$fUnrestricted
000120985 5203_ $$aThe R-RAS2 GTP hydrolase (GTPase) (also known as TC21) has been traditionally considered quite similar to classical RAS proteins at the regulatory and signaling levels. Recently, a long-tail hotspot mutation targeting the R-RAS2/TC21 Gln72 residue (Q72L) was identified as a potent oncogenic driver. Additional point mutations were also found in other tumors at low frequencies. Despite this, little information is available regarding the transforming role of these mutant versions and their relevance for the tumorigenic properties of already-transformed cancer cells. Here, we report that many of the RRAS2 mutations found in human cancers are highly transforming when expressed in immortalized cell lines. Moreover, the expression of endogenous R-RAS2Q72L is important for maintaining optimal levels of PI3K and ERK activities as well as for the adhesion, invasiveness, proliferation, and mitochondrial respiration of ovarian and breast cancer cell lines. Endogenous R-RAS2Q72L also regulates gene expression programs linked to both cell adhesion and inflammatory/immune-related responses. Endogenous R-RAS2Q72L is also quite relevant for the in vivo tumorigenic activity of these cells. This dependency is observed even though these cancer cell lines bear concurrent gain-of-function mutations in genes encoding RAS signaling elements. Finally, we show that endogenous R-RAS2, unlike the case of classical RAS proteins, specifically localizes in focal adhesions. Collectively, these results indicate that gain-of-function mutations of R-RAS2/TC21 play roles in tumor initiation and maintenance that are not fully redundant with those regulated by classical RAS oncoproteins.
000120985 536__ $$9info:eu-repo/grantAgreement/ES/MECD/FPU13-02923$$9info:eu-repo/grantAgreement/ES/MICINN-AEI-FEDER/RTI2018-096481-B-100
000120985 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000120985 590__ $$a6.9$$b2023
000120985 592__ $$a2.334$$b2023
000120985 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b36 / 313 = 0.115$$c2023$$dQ1$$eT1
000120985 593__ $$aCancer Research$$c2023$$dQ1
000120985 591__ $$aONCOLOGY$$b42 / 322 = 0.13$$c2023$$dQ1$$eT1
000120985 593__ $$aMolecular Biology$$c2023$$dQ1
000120985 591__ $$aGENETICS & HEREDITY$$b16 / 191 = 0.084$$c2023$$dQ1$$eT1
000120985 593__ $$aGenetics$$c2023$$dQ1
000120985 591__ $$aCELL BIOLOGY$$b40 / 205 = 0.195$$c2023$$dQ1$$eT1
000120985 594__ $$a15.3$$b2023
000120985 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000120985 700__ $$aFernández-Pisonero, I.
000120985 700__ $$0(orcid)0000-0002-0163-8378$$aMovilla, N.
000120985 700__ $$aLorenzo-Martín, L. F.
000120985 700__ $$aNieto, B.
000120985 700__ $$aAbad, A.
000120985 700__ $$aGarcía-Navas, R.
000120985 700__ $$aLlorente-González, C.
000120985 700__ $$aSánchez-Martín, M.
000120985 700__ $$aVicente-Manzanares, M.
000120985 700__ $$aSantos, E.
000120985 700__ $$aAlarcón, B.
000120985 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía Aznar, J. M.$$uUniversidad de Zaragoza
000120985 700__ $$aDosil, M.
000120985 700__ $$aBustelo, X. R.
000120985 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000120985 773__ $$g42 (2023), [389]–405$$pOncogene$$tONCOGENE$$x0950-9232
000120985 8564_ $$s7562466$$uhttps://zaguan.unizar.es/record/120985/files/texto_completo.pdf$$yVersión publicada
000120985 8564_ $$s2917309$$uhttps://zaguan.unizar.es/record/120985/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000120985 909CO $$ooai:zaguan.unizar.es:120985$$particulos$$pdriver
000120985 951__ $$a2024-07-31-09:40:28
000120985 980__ $$aARTICLE