MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v07/MSV000094814/primaryOK200ProteomicsOliver SchillingQ-ExactiveHomo Sapiens (ncbitaxon:9606)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=92de6c2316dd464cb89a59efa7941959oliver.schilling@mol-med.uni-freiburg.deInstitute of Surgical PathologyMassIVE54UNIMOD:518 - "Diethylation, analogous to Dimethylation."Written Materials, T-cell leukemia, Plasma Membranes, clear cell renal cell adenocarcinoma, Kinship, Clear cell carcinoma of kidney, Organic cation transporter 3, AGL4, Epithelial Mesenchymal Transition, A4, conventional renal cell carcinoma, Tumor, Chromobindins, CCRCC, Social Controls, MAGE-E1 antigen, entry into host via enzymatic degradation of host cuticle, protein polypeptide chains, Life Cycle, establishment and maintenance of substrate location, Annexin IX, mKIAA4049, Extracellular Matrices, Tumor Microenvironments, myd, 9930031C03Rik, gamma sarcoglycan, plant tissue colonization, Hypernephromas, Kinship Network, Tissue, F10N7_150, Mbp-1, proteins, D17Mit170, inner endospore membrane, LYK, Social, clear cell renal cell carcinoma, plasma membrane lipid bilayer, F14D7.2, Role Concepts, invasive growth, Homo sapiens disease, Renal Collecting Duct Carcinoma, Lymphoid, zinc ion regulated proximal promoter sequence-specific DNA binding, Materials Translation, TRANSCRIPTION FACTOR, single organism signaling, Tumors, RNA polymerase II distal enhancer sequence-specific binding, RNA polymerase II core promoter proximal region sequence-specific binding, AnxB9, familial, integral to membrane, Renal Cell Adenocarcinoma, Adenocarcinoma Of Kidney, Tl3, Tl2, Renal Cell Carcinoma, invasion of other organism, DmelCG9968, Collecting Duct Carcinoma of the Kidney, cellular membrane, Clear Cell Renal Cell Carcinoma, Benign, Role Concept, mKIAA0609, EMT, Emt, DAMAGE, Hepatocellular carcinoma-associated protein 1, Role, SPTB2, sarcoglycan, Lymphoid Cell, bacterial inner membrane, CG5730, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, Hypernephroma, Translations, PIG28, Carcinomas, fg, cell membrane, Written Materials Translations, Kidney, PSCTK2, Xanx-4, expanded, F14P3_4, Benign Neoplasms, XAnx4, Nephroid, Controls, Transcription factor, Malignant Neoplasms, Papillary, Nuclear Membrane, MDC1D, enr, Collecting Duct Carcinoma (Kidney), 35kD dystrophin-associated glycoprotein, Cells, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, Extraneuronal monoamine transporter, other neoplasm, Nephroid Carcinoma, metal ion regulated sequence-specific DNA binding, establishment and maintenance of cellular component location, Clear Cell Renal Carcinoma, Adenocarcinoma, Tcsk, big, Regulations, AnxB10, Nuclear Membranes, entry into cell of other organism involved in symbiotic interaction, AnxB11, BcDNA:GH16395, HEL-S-274, Neoplasms, Prognostic Factors, clear cell kidney carcinoma, Renal Adenocarcinomas, SEPALLATA 2, protein-containing complex, Transcription Factor, Calelectrins, large, Hypernephroid, zinc ion regulated core promoter proximal region sequence-specific DNA binding, Cancer Microenvironment, AIV, Gene Products, disease or disorder, host tissue colonization, Hypernephroid Carcinomas, Renal Carcinomas, Hypernephroid Carcinoma, MAM, gamma-SG, EMTH, ANNEXIN A2, Transcription, ERT, ANNEXIN A1, Tissues, MDDGB6, Collecting Duct Carcinoma, LPFS1, Renal, Calcimedin, AI847422, epithelial-mesenchymal transition, Calelectrin, Neoplasias, AI265406, RNA polymerase II proximal promoter sequence-specific DNA binding, Cytoplasmic Membranes, ESX, Extracellular, copper ion regulated proximal promoter sequence-specific DNA binding, Transition, Collecting Duct Carcinomas (Kidney), constitutitional genetic, Grawitz, Cancer, Malignant Neoplasm, cou, Family Research, 35 kDa dystrophin-associated glycoprotein, Cancer., Chromophil Renal Cell Carcinoma, Proteins, disorders, Renal Cell Carcinomas, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, Renal Adenocarcinoma, AL033301, Cell, SGCG, Concept, Family Members, Chromophobe Renal Cell Carcinoma, ANNEXIN, Lr, MT, Spnb2, native protein, Spnb-2, Social Control, Tsk, chemical analysis, Neoplasm, RNA polymerase II transcription factor activity, condition, Epithelial-Mesenchymal Transformation, Cell Membranes, Lymphoid Cells, Ann, primary cancer, DMDA1, other organism invasion, underdeveloped, RGD1560259, increased number, Renal Cell, Cancers, metal ion regulated core promoter proximal region sequence-specific binding, malignant tumor, F10N7.150, Gene Proteins, entry into host cell via penetration peg, localisation, signalling process, Families, Bra, regulation, renal clear cell carcinoma, Relatives, hereditary, Microenvironments, Neoplasia, DmelCG5730, Networks, MGC130048, Collecting Duct, determination, CG9968, Mbp1, protein, Nuclear Envelopes, Papillary Renal Cell Carcinoma, Membrane Tissues, Lipocortins, Adenocarcinoma Of Kidneys, Renal Cell Adenocarcinomas, diseases, Roles, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, Concepts, diseases and disorders, Written, protein aggregate, Formal Social Controls, Family Life Cycle, Annexin, F14D7_2, entry into host via a specialized structure during symbiotic interaction, MXK3.27, increased, human disease, me75, Prognoses, Envelope, membrane region, hypoplasia, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, T1, genetic, Annexin X, malignant neoplasm, HCA1, tissue invasion, plasmalemma, Plasma Membrane, AW106930, AGAMOUS-like 4, gamma-sarcoglycan, MXK3_27, Malignancies, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, associated, Family Life Cycles, Annexin XI, OXY5, Cancer Microenvironments, Membrane Tissue, establishment and maintenance of substance location, Carcinoma, Adenocarcinoma Of, annexin 1, annexin 2, gyltl1b-b, Written Materials Translation, SG-gamma, entry into cell of other organism during symbiotic interaction, jen, Epithelial-Mesenchymal, membranous organ component, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, Adenocarcinomas, clear-cell metastatic renal cell carcinoma, Acute onset, invasion into other organism, single organism localization, MDDGA6, Diseases, entry into host through host barriers, KIAA0609, Filiation, regulator, F14P3.4, membrane of organ, Factors, gyltl1b, Annx, ESE-1, Prognostic, mdc1d, Control, Clear-cell metastatic renal cell carcinoma, gamma (35kDa dystrophin-associated glycoprotein), Renal Cell Cancer, Life Cycles, disease, DMDA, enlarged, Annexin VIII, inherited genetic, ATOXY5, Calcimedins, mMage-e1, Regulation, accessory, metal ion regulated proximal promoter sequence-specific DNA binding, Prognostic Factor, other disease, SGCG_HUMAN, Family Member, Epithelial Mesenchymal Transformation, Microenvironment, entry into other organism during symbiotic interaction, Cytoplasmic Membrane, infiltrating, Renal Cell Cancers, Benign Neoplasm, Calpactins, Matrix, Gene, Network, OCT3, Matrices, EPR-1, Malignant, supernumerary, TYPE, froggy, Gyltl1a, DAGA4, Translation, polypeptide chain, reduced, integral component of membrane, X-anx4, Sarcomatoid Renal Cell Carcinoma, 35DAG, establishment and maintenance of position, CG9579, Low, tiny, SCG3, hypernephroma, Grawitz Tumor, Annexin B9, ZAP36, matrisome, entry into other organism involved in symbiotic interaction, Malignancy, Research, Envelopes, penetration into host via a specialized structure, LARGE, annexin, entry into host via enzymatic degradation of host anatomical structure, elf3, Annexin A8, elf1, non-neoplastic, Materials Translations, Cytoplasmic, BPFD#36, great, region of membrane, mesenchymal cell differentiation from epithelial cell, disorder, Kinship Networks, Family, integral to plasma membrane, Lymphocyte, small, Transformation, membrane, DmelCG9579, Formal Social Control, protein complex, integral component of plasma membrane, Annexin B10, Collecting Duct Carcinomas, Alpha-dystrobrevin-associated MAGE Protein, medical condition, Anx B9, LGMD2C, transcription factor activity, natural protein, Protein, whole membrane, conventional (Clear cell) renal cell carcinoma, establishment and maintenance of localization, Nuclear, Nephroid Carcinomas, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, Plasma, Membranes, transmembrane, distinct, Renal Carcinoma, Annexin A11, Anx4, Translatings, single-organism localization, ANX4, Lipocortin, Membrane, copper ion regulated core promoter proximal region sequence-specific binding, Protein Gene Products, anxX, present in greater numbers in organism, Collecting Duct (Kidney), SCARMD2, penetration into host via a specialized structure during symbiotic interaction, Calpactin, assay, cytoplasmic membraneimprinted and ancient gene protein, Cancer Microenvironments, Membrane Tissue, membrane, transmembrane, membrane of organ, 32-kDa, Cancer., Lipocortin IV, Microenvironment, Calelectrin 32-kDa, Tissues, membrane region, Tissue, integral to membrane, Membrane, membranous organ component, Tumor, Ximpact, Placental Anticoagulant Protein II, impact-a, Calelectrin, Membrane Tissues, Cancer Microenvironment, integral component of membrane, region of membrane, whole membrane, IMPACT, imprinted and ancient gene protein homolog, Calelectrin 32 kDa, Annexin IV, Tumor Microenvironments, E430016J11Rik, Microenvironments, RWDD5, CancerfalseVersatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures and composition of the tumor microenvironmentClear cell renal cell carcinoma (ccRCC) is the most prevalent type of renal malignant disease and is characterized by dismal prognosis in the metastasized setting. Invasive growth of cancer cells relates to high levels of compressive forces translating to relevant damage of the plasma membrane. However, functional implications of protein machineries required for plasma membrane repair in ccRCC are not yet completely elucidated. Given the membrane-associated localization of the large family of annexin proteins, we aimed for a global annotation annexin proteins, which led to the identification of ANXA4 selectively expressed in cancer cells of ccRCC. Interestingly, ANXA4 showed context-dependent distinct localization patterns including the plasma membrane as well as the nuclear compartment/nuclear membrane. We investigated the functional role of ANXA4 in ccRCC employing genetic titration studies (knockdown, CRISPR/Cas9 knockout and overexpression) and identified impaired acute plasma membrane repair as well as invasive capability in conditions of reduced ANXA4 expression. Utilizing computational segmentation of the tumor microenvironment (TME) of ccRCC samples revealed that ANXA4 low tumors exhibited a distinct TME composition compared to ANXA4 high cases. ANXA4 low tumors showed higher levels of tumor infiltrating lymphocytes accompanied by increased deposition of acellular extracellular matrix. Further transcriptomic analysis demonstrated major alterations in transcriptional signatures related to epithelial-mesenchymal transition (EMT) and immune signaling. Transcription factor enrichment analysis and further functional validation identified ELF3 as one central regulator of invasive properties. Our integrative approach including molecular analyses with advanced histopathological segmentation uncovered novel roles for ANXA4 in modulating acute membrane repair, transcriptional regulation, and shaping cellular composition of the ccRCC tumor microenvironment.Tue May 21 02:03:00 BST 2024MSV000094814