January, 2023
Through data mining strategies, we discovered that PREX1 integrates a signaling axis, indicative of tumors with myeloid infiltration and tumor angiogenesis, that correlated with lower survival of low-grade glioma patients. This research is part of the doctoral work of Yarely Mabell Beltrán-Navarro and was published in Frontiers in Oncology.
We demonstrated that ARHGEF17 contributes to metastatic dissemination of lung cancer cells in immunocompetent mice. This RhoGEFs participates in the invasive and migratory responses elicited by Gi protein-coupled LPA receptors. The Gbetagamma signaling complex recruits ARHGEF17 to the cell periphery and actin fibers. Mechanistically, ARHGEF17 is activated by Gbetagamma by the removal of inhibitory intramolecular restrictions. This investigation was part of the doctoral work of Irving García-Jiménez. It was published in the Journal of Biological Chemistry. Irving continued his career as a Postdoctoral Fellow at the National Cancer Institute in Bethesda, MD, USA.
Our investigation on the mechanism by which Gbetagamma contributes to chemotactic cell migration revealed that this signaling heterodimer activates the RacGEF P-Rex1 by a two-step mechanism based on independent interaction interfaces to recruit and unroll this RacGEF. These findings are part of Daniel Cervantes-Villagrana’s postdoctoral work and were published in BBRC.
As part of his doctoral work, Alejandro Castillo-Kauil discovered PDZ-RhoGEF as a new signaling effector of Galpha-s which enables the GEF to activate Cdc42 and promote endothelial cell sprouting. These findings extend the knowledge about the conventional mechanism by which this RhoGEF is activated by Galpha-13 to promote actin stress fibers via Rho. This work was published in the Journal of Biological Chemistry. For this work, Alejandro received the JBC’s early career investigator Tabor Award and got the opportunity to continue his career as Postdoctoral Fellow at the Barts Cancer Institute in London, UK.
Víctor Manuel Color-Aparicio completed his doctoral work investigating the mechanisms of endothelial cell sprouting by RhoJ and its activation by Intersectin-1. Endothelial cell sprouting is a critical event in tumor-induced angiogenesis. This work was published in BBRC.
January, 2020
Our paper: “cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits” has been selected as the representative ‘Signal transduction’ article for the 2019 retrospective collection called “The year in JBC: 2019.” According to the communication received: "The associate editors looked through hundreds of papers to come up with what they felt best represented the exciting advances reported in JBC last year" The special issue can be found at http://www.jbc.org/site/vi/.
December, 2019
On December 13th, Raúl Vega-Fonseca successfully presented his dissertation obtaining his Masters in Science degree in Pharmacology. Raúl presented the thesis "Chemotactic signaling by GPCRs: Galpha-interacting proteins as potential Ggetagamma regulators".
November, 2019
Yarely Mabell Beltrán Navarro successfully presented her Ph.D. project which aims to characterize P-REX1, a multidomain GEF, as a scaffold and effector of the G-PI3K-mTORC2-AKT signaling pathway that participates in cell migration. Understanding this macromolecular complex will set the basis for pharmacological intervention aiming to control aberrant cell migration.
October, 2019
Yazmin Torres-Santos, a graduate of Universidad Veracruzana, joined our group to do her Master's work. Her project will be focused on the S1P1 / P-REX1 / Rac1 axis investigating how P-Rex1 establishes a circuit that regulates the magnitude and temporality of sphingosine-1-phosphate receptors signaling.
June, 2019
June 28th, 2018. Sendi Rafael Adame-Garcia obtained his Ph.D. in Cell Biology. His work was codirected by Dr. Guadalupe Reyes-Cruz. He will continue as a posdoc in our group. Click here to see Sendi's publications as Ph.D. student. Among Sendi's publications, the work: Adame-García et al. 2019. cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits. J Biol Chem. 294 (7): 2232-2246 was selected in the Journal of Biological Chemistry as one of the Editor's pick and Sendi Adame-García's academic profile was published at the Journal of Biological Chemistry web page. According to the editor's message, this distinction is reserved for 2% of JBC's articles, thus being highlighted for their importance. During his studies, Sendi obtained a PROLAB grant, given by the ASBMB/IUBMB/PABMB to support a six-month work visit to Susan S. Taylor's laboratory at the University of California, San Diego.
April, 2019
Recent publications from our group:
1. Adame-García et al. 2019. cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits. J Biol Chem. 294(7):2232-2246. This work was highligted as an Editor's pick and Sendi Adame García's academic profile was published at The Journal of Biological Chemistry's web page.
2. Cervantes-Villagrana et al. 2019. Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. J Biol Chem. 294(2):531-546.
3. Cervantes-Villagrana et al. 2019. Protumoral bone marrow-derived cells migrate via Gβγ-dependent signaling pathways and exhibit a complex repertoire of RhoGEFs. J Cell Commun Signal. Jan 5. doi: 10.1007/s12079-018-00502-6.
Published our recent collaboration with Evi Kosteni's group:
Annala et al. 2019. Direct targeting of Gαq and Gα11 oncoproteins in cancer cells. Science Signaling. 12(573). pii: eaau5948. doi: 10.1126/scisignal.aau5948 Community outreach, video and press release (in Spanish): Daniel Cervantes-Villagrana described his doctoral work in an interview for Conexion Cinvestav available here and at the Conexion's YouTube Channel here. Read here our press release regarding Daniel's work. .
December, 2018
December 7th, 2018. Yarely Mabell Beltrán Navarro graduated as a Master in Science in Pharmacology. She will continue as a Ph. D. student in our group.
December 14th, 2018. Daniel Cervantes-Villagrana obtained his Ph.D. in Pharmacology. He will continue as a posdoc in our group. Click here to see Daniel's publications as Ph.D. student.
November, 2018
Raúl Vega Fonseca joined our group to do his Master's work. He successfully presented his project: "Cell migration promoted by GPCRs through Gbg is controlled by effectors and regulators of Ga subunits that influence the dissociation of heterotrimeric G proteins"..
December 8, 2017
José Vázquez-Prado participated as speaker at the Cellular Signaling in Cancer symposium that took place on April 12 at UNAM, at the Chemistry Institute. The video of the symposium, available on YouTube, can be seen here, the presentation of our work begins at 1:04:00 of the video.
April 12, 2018
Our basic science project: "Molecular mechanisms of endothelial cell migration and angiogenesis" was approved by Conacyt.
December 4, 2017
Alejandro Castillo-Kauil began a 5-month work visit at Heidi Welch's laboratory at the Babraham Institute in Cambridge, England.Heidi Welch is the discoverer of <ahref="http:>P-Rex1 , a GEF that activates the Rac GTPase. P-Rex1 has been the protagonist of several of our studies focused on understanding cell migration regulated by G protein-coupled receptors.
November, 2017
Yarely Mabell Beltrán Navarro joined our group to do her Master's work. She successfully presented her project: "P-Rex1 as signaling platform and effector of the Gbetagama-PI3Kgama-mTORC1/2 signaling pathway".
November, 2017
Our webpage includes a new section entitled LabSignalingPathways which includes drawings by members of our team illustrating diverse signaling cascades including our current working hypotheses.
October, 2017
Our group had a significant participation in the VI Congress of the Signal Transduction Branch of the Mexican Biochemical Society held in Puerto Vallarta, Jalisco. José Vázquez-Prado presented the conference: "RhoGEFs as signaling platforms of chemotactic GPCRs". In the Signaling and Cancer session, Daniel Cervantes-Villagrana presented: "Constitutively active Galpha-q and Galpha-13 mutants maintain stable interactions with Gbetagamma inhibiting the activation of its chemotactic effectors" and in the Signaling Effectors session, Sendi Rafael Adame-García presented the work: "cAMP Promotes Rac Activation and Cell Migration via P-Rex1: A Novel Effector of PKA Regulatory Subunits". In the poster session, Irving García-Jiménez presented: "Mechanisms of Regulation of ARHGEF17, a Tumor Endothelial Marker (TEM4)".
June 30, 2016
Magda Hernández-Vásquez obtained the Ph.D. in Pharmacology. Her work: "Characterization of the signal transduction mechanisms of the Tumor Endothelial Marker 5 (TEM5/GPR124) in the angiogenic process" was published in the Journal of Biological Chemistry. Congratulations to Magda and good luck with her new projects.
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June 20, 2017. Published Papers:
J Biol Chem. 2017 Jun 9: Cell adhesion controlled by adhesion G-protein coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising Intersectins and Elmo/Dock. Hernández-Vásquez MN, Adame-García SR, Hamoud N, Chidiac R, Reyes-Cruz G, Gratton JP, Côté JF, Vázquez-Prado J..
Biochim Biophys Acta. 2017 May 26: Zonula occludens-2 regulates Rho proteins activity and the development of epithelial cytoarchitecture and barrier function. Raya-Sandino A, Castillo-Kauil A, Domínguez-Calderón A, Alarcón L, Flores-Benitez D, Cuellar-Perez F, López-Bayghen B, Chávez-Munguía B, Vázquez-Prado J, González-Mariscal L.
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May 25, 2017
José Vázquez Prado visited the Institute of Physics of the UASLP where he presented the seminar: "RhoGEFs as signaling platforms for chemotactic receptors".
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May 23, 2017
Claire Wells, a researcher at King's College London, visited our laboratory and presented the seminar "Cancer cell adhesion dynamics, specific role for PAK4" to the Cinvestav community. In addition, together with Rajandeep Singh, KCL's Liaison Officer officer for Latin America, they promoted links through the forum: "Developing connections in Mexico to support research and education".
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March, 2017
Jose Vazquez-Prado visited Heidi Welch's lab at the Babraham Institute in Cambridge. He gave the seminar "RhoGEFs as signaling platforms of chemotactic GPCRs" and discussed collaborative projects and plans for student's mobility to the Signalling group at the Babraham Institute.
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December 14, 2016
Irving García-Jiménez obtained his Master's Degree in Pharmacology. Irving studied the regulatory mechanisms of ARHGEF17, a tumor endothelial marker, demonstrating that this is a GPCR-regulated RhoGEF whose activation depends on changes in their localization and intramolecular interactions in response to angiogenic factors.
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November 21st, 2016
Sendi Rafael Adame-Garcia began a work visit at the University of California at San Diego (UCSD). For six months, Sendi will work at the laboratories of Susan S. Taylor and Silvio Gutkind investigating, as part of their doctoral thesis, the mechanisms by which the protein kinase A regulatory subunit modulates the RacGEF P-Rex1, promoting cell migration.
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November, 2016
On November 4, Prof. José Vázquez-Prado gave the seminar: "Signal Transduction pathways that activate the molecular switches relevant to cell migration in tumor angiogenesis " at CICY (Center for Scientific Research of Yucatan).
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October, 2016
Published Papers:
1. Vazquez-Prado et al 2016. Gbetagamma pathways in cell polarity and migration linked to oncogenic GPCR signaling: potential relevance in tumor microenvironment Mol Pharmacol. 2016 Sep 16. pii: mol.116.105338
2. Hernández-Bedolla, et al. 2016. Calcium-sensing-receptor (CaSR) controls IL-6 secretion in metastatic breast cancer MDA-MB-231 cells by a dual mechanism revealed by agonist and inverse-agonist modulators. Mol Cell Endocrinol. Nov 15;436:159-68.
3. Mejía-Rangel et al. 2016. Pro-adhesive phenotype of normal endothelial cells responding to metastatic breast cancer cell conditioned medium is linked to NFκB-mediated transcriptomic regulation. Int J Oncol. Sep 26: 2173-2185
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June 30, 2016
Lydia Chavez Vargas and Ricardo Hernández García obtained the Ph.D. in Pharmacology on 30 June. Lydia 's work : "Molecular aspects of the interaction between Protein Kinase A and the RacGEF P-Rex1 and its relevance in angiogenic signaling pathways" was published in the Journal of Biological Chemistry. Ricardo 's work : "Endothelial RhoGEFs: systematic analysis of its expression profile in tumor endothelial cells and stimulated with VEGF" was published in Vascular Pharmacology. Congratulations to both and good luck in their new projects.
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May, 2016
On may 13, José Vázquez-Prado PhD gave the seminar "RhoGEFs as integrators of oncogenic signals" at the Cell Physiology Institute of the Autonomous National University of Mexico. The seminar can be viewed online following this hyperlink.
During his presentation, Vázquez-Prado PhD spoke about the involvement of RhoGEFs in angiogenic transduction signals and their role as intermediary in the activation of GTPases by G protein coupled receptors; as well as its expression in tumor endothelial cells and bone marrow cells that contribute to tumor development.
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March, 2016
Alberto Cervantes Villagrana PhD, professor and researcher from Autonomus University of Zacatecas, visited our laboratory during the last week of February. We had the opportunity to share the strategies that we are using to study the development of tumors in murine models and consider the possibility of future interactions between our research groups.
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February 10,2016
Published Paper:
Protein kinase A (PKA) Type I interacts with P-Rex1, a Rac guanine nucleotide exchange factor: Effect on PKA localization and P-Rex1 signaling.
Chávez-Vargas L, Adame-García SR, Cervantes-Villagrana RD, Castillo-Kauil A, Bruystens JG, Fukuhara S, Taylor SS, Mochizuki N, Reyes-Cruz G, Vázquez-Prado J. J Biol Chem. 2016 Jan 21. pii: jbc.M115.712216.
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February 2016
José Vázquez Prado PhD gave a seminar at HRAEB (Regional Hospital of High Specialty of Bajío) in León, Guanajuato. He presented the progress of our studies with murine models of cancer concerning the role of the bone marrow in tumor growth, with emphasis on the action of RhoGEFs in this process. The seminar was followed by a meeting with clinical oncologists, pathologists and researchers from HRAEB to discuss a plan of collaboration to investigate the expression and activity of RhoGEFs in cancer patients.
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January 2016
Magda Hernandez-Vasquez initiated work visit to the laboratory of Jean-François Côté at IRCM in Montreal. Magda will spend six-months doing experiments related to the signal transduction mechanisms of GPR124/TEM5, a GPCR originally described as a tumor endothelium marker, the central theme of her doctoral thesis.
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December 2015
Victor Manuel Color Aparicio got his Master degree in Pharmacology. His work identified 2 RhoGEFs (ITSN1 and ARHGEF1) that in an active form, promote the activation of RhoJ, a GTPasa with clinical relevance in tumor angiogenesis. The active form of RhoJ promotes the formation of filopodia, structures that perceived angiogenic processes signals during cell migration, it determined the RhoJ activation in a pronounced form by conditioned tumor means in endothelial cells.
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November 23rd, 2015
The paper of Ricardo Hernández García, PhD student, has been published in Vascular Pharmacology journal.
Endothelial RhoGEFs: A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells.
Hernández-García R, Iruela-Arispe ML, Reyes-Cruz G, Vázquez-Prado J. Vascul Pharmacol. 2015 Oct 17. pii: S1537-1891(15)00220-7. doi: 10.1016/j.vph.2015.10.003.
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November 11th, 2015
Irving García Jiménez, graduated from the Universidad Autónoma de Guerrero, joined to our group to begin his master´s studies. He will be working about a regulatory mechanisms of ARHGEF17, a RhoGEF whose expression is increased in tumor endothelium.
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April 7th, 2015
We recently moved to the newly renovated facilities of the Laboratory of Signal Transduction in Angiogenesis. The new area of approximately 120 square meters includes a main laboratory room with designated workspaces and desks for seven students, a research assistant and a technician. Besides, we count with a microscopy room, a darkroom, two cell culture rooms with biosafety hoods, and specific areas for molecular biology and microbiology procedures. Additionally, the main room has a lateral accessory bench for common equipment like microcentrifuges, PCR machines, photo documentation system, shakers, etc. Importantly, to promote informal discussions, there is a small spot with a board next to the office.
The new lab was designed having in mind the requirements of each member of our group. The common work areas were defined according to the methodologies that we commonly use (cell culture, visualization of fluorescent proteins in cells, lentivirus, recombinant bacteria and proteins, electrophoretic analysis of proteins and nucleic acids, immuno-detection of proteins and macromolecular complexes, extraction and analysis of samples of tumor tissue, among others). The goal is to keep the best possible conditions to facilitate the progress of each individual project and the interactions among all members of our group, in a pleasant work atmosphere with a nice view to the gardens.
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December 18 , 2014
Evelyn Robles Molina earned her PhD in Pharmacology. Her work revealed a novel mechanism that regulates mTOR kinase signaling by G protein coupled receptors. Evelyn demonstrated that Gbetagamma heterodimer directly interacts with mTOR, promoting the activation of mTORC1 and mTORC2 complexes, constituting a new regulatory node in the PI3K/AKT/mTOR pathway.
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October, 2014
Victor Manuel Color-Aparicio, graduated from Universidad Michoacana de San Nicolás de Hidalgo, joined our group for his Master's thesis. Victor will identity potential activators of RhoJ, a GTPase recently described as a critical participant of tumor-induced angiogenesis.
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Rodolfo Daniel Cervantes-Villagrana, PhD student, won Cinvestesis 180 a contest aimed to recognize the best presentation of a doctoral thesis project in 180 seconds, in an understandable manner to general audiences. Daniel competed with more than 80 doctoral students. The jury was composed of experts in scientific communication and Cinvestav researchers. Daniel 's project aims to characterize the role of bone marrow cells in cancer, with emphasis on the participation of RhoGEFs expressed in endothelial progenitor cells.
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June, 2014
Grant approved by CONACyT to establish a system for bone marrow reconstitution in models of tumor-induced angiogenesis. The system will also benefit groups working on diverse aspects of cancer, immunology, development and stem cells, among others.
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April 3rd, 2014
Ismael Bracho-Valdés received his Ph.D. in Pharmacology. His work focused on the regulation of the PI3K/AKT/mTOR signaling pathway by newly identified interacting proteins.
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Feb, 2014. Published Paper:
Gbetagamma interacts with mTOR and promotes its activation.
Robles-Molina E, Dionisio-Vicuña M, Guzmán-Hernández ML, Reyes-Cruz G, Vázquez-Prado J. Biochem Biophys Res Commun. 2014 Feb 7;444(2):218-23
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