295:(EMT) maintenance in vitro, which is known to correlate well with metastasis in vivo. The authors showed that the metastatic potential of oncogenic mammary epithelial cells required an autocrine PDGF/PDGFR signaling loop, and that cooperation of autocrine PDGFR signaling with oncogenic was required for survival during EMT. Autocrine PDGFR signaling also contributes to maintenance of EMT, possibly through activation of STAT1 and other distinct pathways. In addition, expression of PDGFRα and -β correlated with invasive behavior in human mammary carcinomas. This indicates the numerous pathways through which autocrine signaling can regulate metastatic processes in a tumor.
237:
overexpression occurs in approximately a quarter of breast cancers and correlates with poor prognosis. Recent research revealed that IL-6 secretion induced by HER2 overexpression activated STAT3 and altered gene expression, resulting in an autocrine loop of IL-6/STAT3 expression. Both mouse and human
271:
and through autocrine signaling on carcinoma cells. Evidence shows that autocrine VEGF is involved in two major aspects of invasive carcinoma: survival and migration. Moreover, it was shown that tumor progression selects for cells that are VEGF-dependent, challenging the belief that VEGF's role in
328:
In HER2 overexpressing breast cancers, the HER2–IL-6–STAT3 signaling relationship could be targeted to develop new therapeutic strategies. HER2 kinase inhibitors, such as lapatinib, have also demonstrated clinical efficacy in HER2 overexpressing breast cancers by disrupting a neuregulin-1
238:
in vivo models of HER2-overexpressing breast cancers relied critically on this HER2–IL-6–STAT3 signaling pathway. Another group found that high serum levels of IL-6 correlated with poor outcome in breast cancer tumors. Their research showed that autocrine IL-6 signaling induced
790:
Buffière A, Uzan B, Aucagne R, Hermetet F, Mas M, Nassurdine S, Aznague A, Carmignac V, Tournier B, Bouchot O, Ballerini P, Barata JT, Bastie JN, Delva L, Pflumio F, Quéré R (November 2019). "T-cell acute lymphoblastic leukemia displays autocrine production of
Interleukin-7".
127:, growth, and survival. One approach used by tumors to upregulate growth and survival is through autocrine production of growth and survival factors. Autocrine signaling plays critical roles in cancer activation and also in providing self-sustaining growth signals to tumors.
316:
interactions of the Wnt pathway. In addition, VEGF-A production and VEGFR-2 activation on the surface of breast cancer cells indicates the presence of a distinct autocrine signaling loop that enables breast cancer cells to promote their own growth and survival by
303:
The growing knowledge behind the mechanism of autocrine signaling in cancer progression has revealed new approaches for therapeutic treatment. For example, autocrine Wnt signaling could provide a novel target for therapeutic intervention by means of Wnt
1064:
Marek, Lindsay; Ware, Kathryn E.; Fritzsche, Alexa; Hercule, Paula; Helton, Wallace R.; Smith, Jennifer E.; McDermott, Lee A.; Coldren, Christopher D.; Nemenoff, Raphael A.; Merrick, D. T.; Helfrich, B. A.; Bunn Jr, P. A.; Heasley, L. E. (2008).
187:, interference with the de-regulated Wnt signaling pathway reduces proliferation and survival of cancer. These findings suggest that interference with Wnt signaling at the ligand-receptor level may improve the effectiveness of cancer therapies.
417:
expression are increased in response to tamoxifen in human breast cancer cells. In a recent study, one group showed that STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting
740:
Sansone, Pasquale; Storci, Gianluca; Tavolari, Simona; Guarnieri, Tiziana; Giovannini, Catia; Taffurelli, Mario; Ceccarelli, Claudio; Santini, Donatella; Paterini, Paola; Marcu, Kenneth B.; Chieco, Pasquale; Bonafè, Massimiliano (2007).
250:
A study demonstrates how the autocrine production of the IL-7 cytokine mediated by T-cell acute lymphoblastic leukemia (T-ALL) can be involved in the oncogenic development of T-ALL and offer novel insights into T-ALL spreading.
839:
Weigand, Melanie; Hantel, Pia; Kreienberg, Rolf; Waltenberger, Johannes (2005). "Autocrine vascular endothelial growth factor signaling in breast cancer. Evidence from cell lines and primary breast cancer cultures in vitro".
222:. Several studies have outlined the importance of autocrine IL-6 signaling in lung and breast cancers. For example, one group found a positive correlation between persistently activated tyrosine-phosphorylated
95:
receptors are replaced by "high-affinity" IL-2 receptors consisting of α, β, and γ chains. The cell then releases IL-2, which binds to its own new IL-2 receptors, causing self-stimulation and ultimately a
638:
Gao, Sizhi Paul; Mark, Kevin G.; Leslie, Kenneth; Pao, William; Motoi, Noriko; Gerald, William L.; Travis, William D.; Bornmann, William; Veach, Darren; Clarkson, Bayard; Bromberg, Jacqueline F. (2007).
406:(FGFs) and FGF receptors in NSCLC cell lines, and found that FGF2, FGF9 and their receptors encompass a growth factor autocrine loop that is active in a subset of gefitinib-resistant NSCLC cell lines.
26:
in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with
1114:
Yi, Eun Hee; Lee, Chang Seok; Lee, Jin-Ku; Lee, Young Ju; Shin, Min Kyung; Cho, Chung-Hyun; Kang, Keon Wook; Lee, Jung Weon; Han, Wonshik; Noh, D.-Y.; Kim, Y.-N.; Cho, I.-H.; Ye, S.-k. (2012).
398:
have shown limited therapeutic success. This resistance is proposed to be because autocrine growth signaling pathways distinct from EGFR are active in NSCLC cells.
691:
Hartman, Zachary C.; Yang, Xiao-Yi; Glass, Oliver; Lei, Gangjun; Osada, Takuya; Dave, Sandeep S.; Morse, Michael A.; Clay, Timothy M.; Lyerly, Herbert Kim (2011).
434:
is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior or differentiation of nearby cells.
359:(TNFα). In response to autocrine TNFα signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.
422:
cleavage. These mechanisms of STAT3-RANTES autocrine signaling suggest a novel strategy for management of patients with tamoxifen-resistant tumors.
343:
In addition, drugs may be developed that activate autocrine signaling in cancer cells that would not otherwise occur. For example, a small-molecule
1194:
883:
Mercurio, Arthur M; Bachelder, Robin E; Bates, Richard C; Chung, Jun (2004). "Autocrine signaling in carcinoma: VEGF and the α6β4 integrin".
276:. Instead, this research suggests that VEGF receptor-targeted therapeutics may impair cancer survival and invasion as well as angiogenesis.
1167:
1015:
Petersen, Sean L.; Wang, Lai; Yalcin-Chin, Asligul; Li, Lin; Peyton, Michael; Minna, John; Harran, Patrick; Wang, Xiaodong (2007).
548:"Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation"
481:
226:(pSTAT3), found in 50% of lung adenocarcinomas, and IL-6. Further investigation revealed that mutant EGFR could activate the
287:
is a major cause of cancer deaths, and strategies to prevent or halt invasion are lacking. One study showed that autocrine
1441:
976:"Neuregulin-1-Mediated Autocrine Signaling Underlies Sensitivity to HER2 Kinase Inhibitors in a Subset of Human Cancers"
1409:
260:
1187:
292:
164:
80:
76:
1067:"Fibroblast Growth Factor (FGF) and FGF Receptor-Mediated Autocrine Signaling in Non-Small-Cell Lung Cancer Cells"
693:"HER2 Overexpression Elicits a Proinflammatory IL-6 Autocrine Signaling Loop That is Critical for Tumorigenesis"
641:"Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas"
743:"IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland"
163:. Genetic alterations that lead to de-regulation of the autocrine Wnt pathway result in transactivation of
1574:
1436:
1180:
356:
1255:
1238:
1221:
391:
387:
144:
1451:
1446:
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1116:"STAT3-RANTES Autocrine Signaling is Essential for Tamoxifen Resistance in Human Breast Cancer Cells"
413:
resistance is another major therapeutic problem. It has been shown that phosphorylation of STAT3 and
403:
399:
1543:
1233:
1161:
1017:"Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis"
351:/Diablo that counteracts the inhibition of apoptosis has been shown to enhance apoptosis caused by
172:
1371:
1343:
1270:
1250:
379:
313:
58:
473:
467:
1383:
1356:
1157:
546:
Schlange, Thomas; Matsuda, Yutaka; Lienhard, Susanne; Huber, Alexandre; Hynes, Nancy E (2007).
352:
57:. When interleukin-1 is produced in response to external stimuli, it can bind to cell-surface
1509:
1471:
1351:
1297:
1275:
1228:
136:
974:
Wilson, Timothy R.; Lee, Diana Y.; Berry, Leanne; Shames, David S.; Settleman, Jeff (2011).
340:
are both approaches being explored to therapeutically interference with metastasis in mice.
1480:
1476:
1428:
100:
population of T cells. These T cells can then go on to perform effector functions such as
8:
1538:
1521:
1207:
922:
500:
Bafico, Anna; Liu, Guizhong; Goldin, Luba; Harris, Violaine; Aaronson, Stuart A. (2004).
431:
305:
264:
27:
921:
Jechlinger, M.; Sommer, A; Moriggl, R; Seither, P; Kraut, N; Capodiecci, P; Donovan, M;
171:, for example, mutations in APC, axin, or β-catenin promote β-catenin stabilization and
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502:"An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells"
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155:, inducing its degradation. De-regulation of the autocrine Wnt signaling pathway via
896:
869:
167:(EGFR) and other pathways, in turn contributing to proliferation of tumor cells. In
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and activation of VEGFR-2. This autocrine loop is another example of an attractive
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signals from previously neglected autocrine loops, causing tumor recurrence.
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50:
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through inactivation of a protein complex containing the tumor suppressors
109:
84:
1168:"Autocrine versus juxtacrine signaling modes" - illustration at sysbio.org
140:
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in APC and Axin have been linked to activation of various types of human
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101:
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47:
1305:
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72:
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105:
65:
927:"Autocrine PDGFR signaling promotes mammary cancer metastasis"
920:
739:
288:
223:
176:
120:
545:
882:
789:
234:
148:
88:
71:, i.e., when a T cell is induced to mature by binding to a
1063:
1014:
599:"Autocrine IL-6 Signaling: A Key Event in Tumorigenesis?"
1202:
263:(VEGF). VEGF, produced by carcinoma cells, acts through
259:
Another agent involved in autocrine cancer signaling is
230:
STAT3 pathway via upregulated IL-6 autocrine signaling.
151:. This destruction complex normally triggers β-catenin
91:
costimulatory signal. Upon activation, "low-affinity"
499:
332:
In the case of PDGFR signalling, overexpression of a
298:
973:
690:
1566:
637:
596:
123:development is a complex process that requires
378:For example, despite widespread expression of
1188:
472:. Lippincott Williams & Wilkins. p.
242:features in Notch-3 expressing mammospheres.
597:Grivennikov, Sergei; Karin, Michael (2008).
367:Recent studies have reported the ability of
1113:
783:
469:Introduction To The Pharmaceutical Sciences
1195:
1181:
362:
279:
1160:at the U.S. National Library of Medicine
1131:
1090:
1040:
991:
950:
766:
716:
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614:
573:
563:
517:
1107:
1057:
336:PDGFR or application of the cancer drug
46:An example of an autocrine agent is the
834:
832:
830:
541:
539:
537:
308:or other molecules that interfere with
1567:
1008:
967:
916:
914:
465:
202:that is important for many aspects of
1176:
686:
684:
495:
493:
409:In breast cancer, the acquisition of
291:signaling plays an essential role in
130:
876:
827:
733:
534:
402:revealed the prevalence of specific
81:professional antigen-presenting cell
64:Another example occurs in activated
1442:Transcription preinitiation complex
911:
631:
590:
61:on the same cell that produced it.
13:
1410:Signal transducing adaptor protein
681:
490:
459:
299:Development of therapeutic targets
261:vascular endothelial growth factor
14:
1586:
1151:
931:Journal of Clinical Investigation
747:Journal of Clinical Investigation
645:Journal of Clinical Investigation
382:receptors (EGFRs) and EGF family
293:epithelial-mesenchymal transition
329:(NRG1)-mediated autocrine loop.
165:epidermal growth factor receptor
897:10.1016/j.semcancer.2003.09.016
925:; Beug, H; Grünert, S (2006).
108:activation, and cell-mediated
16:Signaling within the same cell
1:
1133:10.1158/1541-7786.MCR-12-0217
709:10.1158/0008-5472.CAN-11-0308
453:
7:
425:
357:tumor necrosis factor alpha
355:through autocrine-secreted
179:encoding cancer-associated
41:
10:
1591:
885:Seminars in Cancer Biology
466:Pandit, Nikita K. (2007).
392:tyrosine kinase inhibitors
388:non-small-cell lung cancer
139:leads to stabilization of
1494:
1464:
1427:
1402:
1379:
1370:
1342:
1296:
1289:
1214:
1120:Molecular Cancer Research
1033:10.1016/j.ccr.2007.08.029
993:10.1016/j.ccr.2011.07.011
854:10.1007/s10456-005-9010-0
805:10.1038/s41388-019-0921-4
616:10.1016/j.ccr.2007.12.020
519:10.1016/j.ccr.2004.09.032
404:fibroblast growth factors
400:Gene expression profiling
115:
1522:Neuroendocrine signaling
1162:Medical Subject Headings
371:cancer cells to acquire
183:. Furthermore, in human
34:signaling, or classical
390:(NSCLC), EGFR-specific
380:epidermal growth factor
363:Role in drug resistance
280:Promotion of metastasis
254:
245:
190:
1384:cAMP-dependent pathway
1083:10.1124/mol.108.049544
1071:Molecular Pharmacology
552:Breast Cancer Research
353:chemotherapeutic drugs
1510:Synaptic transmission
1506:Neurocrine signaling
1429:Transcription factors
1276:PI3K/AKT/mTOR pathway
272:cancer is limited to
198:(acronym: IL-6) is a
137:Wnt signaling pathway
1575:Signal transduction
1539:Mechanotransduction
1527:Exocrine signalling
1334:Signaling molecules
1208:Signal transduction
1158:Autocrine+signaling
432:Paracrine signaling
265:paracrine signaling
28:paracrine signaling
20:Autocrine signaling
1549:Ion channel gating
1281:Integrin receptors
1215:Signaling pathways
323:therapeutic target
131:In the Wnt pathway
1562:
1561:
1544:Phototransduction
1502:Intracrine action
1460:
1459:
1423:
1422:
1311:Neurotransmitters
753:(12): 3988–4002.
483:978-0-7817-4478-2
334:dominant-negative
269:endothelial cells
169:colorectal cancer
1582:
1515:Chemical synapse
1415:Scaffold protein
1377:
1376:
1372:Second messenger
1298:Receptor ligands
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943:10.1172/JCI24652
918:
909:
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873:
836:
825:
824:
799:(1): 7357–7365.
787:
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770:
759:10.1172/JCI32533
737:
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730:
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688:
679:
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657:10.1172/JCI31871
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448:Endocrine system
208:immune responses
204:cellular biology
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1394:Lipid signaling
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923:Cordon-Cardo, C
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912:
881:
877:
837:
828:
788:
784:
738:
734:
703:(13): 4380–91.
697:Cancer Research
689:
682:
651:(12): 3846–56.
636:
632:
595:
591:
565:10.1186/bcr1769
544:
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319:phosphorylation
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1329:Growth factors
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1204:Cell signaling
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1152:External links
1150:
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1147:
1106:
1077:(1): 196–207.
1056:
1007:
966:
937:(6): 1561–70.
910:
875:
848:(3): 197–204.
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732:
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589:
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512:(5): 497–506.
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369:drug-resistant
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135:Normally, the
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1357:Intracellular
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1030:
1027:(5): 445–56.
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986:(2): 158–72.
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891:(2): 115–22.
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218:, as well as
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196:Interleukin 6
188:
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185:breast cancer
182:
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173:transcription
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125:cell division
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51:interleukin-1
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22:is a form of
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1554:Gap junction
1389:Ca signaling
1352:Cell surface
1126:(1): 31–42.
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110:cytotoxicity
104:activation,
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1465:By distance
1403:Assistants:
1362:Co-receptor
1021:Cancer Cell
980:Cancer Cell
603:Cancer Cell
506:Cancer Cell
306:antagonists
233:Similarly,
83:and by the
69:lymphocytes
38:signaling.
1532:Pheromones
1472:Juxtacrine
609:(1): 7–9.
558:(5): R63.
454:References
438:Intracrine
285:Metastasis
206:including
102:macrophage
98:monoclonal
32:intracrine
1486:Endocrine
1481:Paracrine
1477:Autocrine
1344:Receptors
1324:Cytokines
821:199668368
411:tamoxifen
396:gefitinib
373:mitogenic
240:malignant
228:oncogenic
216:apoptosis
157:mutations
141:β-catenin
59:receptors
55:monocytes
36:endocrine
1569:Category
1306:Hormones
1256:JAK-STAT
1244:MAPK/ERK
1239:TGF beta
1142:23074171
1101:18849352
1051:17996648
1002:21840482
961:16741576
905:15018895
870:25711624
862:16328160
813:31417180
793:Oncogene
777:18060036
727:21518778
675:18060032
625:18167335
584:17897439
528:15542433
426:See also
394:such as
314:receptor
200:cytokine
181:proteins
48:cytokine
42:Examples
1437:General
1261:Akt/PKB
1092:2669785
1042:3431210
952:1469776
768:2096439
718:3129398
666:2096430
575:2242658
420:caspase
384:ligands
345:mimetic
73:peptide
1290:Agents
1164:(MeSH)
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415:RANTES
338:STI571
310:ligand
161:cancer
116:Cancer
106:B cell
66:T cell
1452:TFIIH
1447:TFIID
1271:Hippo
1251:Notch
866:S2CID
817:S2CID
289:PDGFR
224:STAT3
177:genes
121:Tumor
1222:GPCR
1138:PMID
1097:PMID
1047:PMID
998:PMID
957:PMID
901:PMID
858:PMID
809:PMID
773:PMID
723:PMID
671:PMID
621:PMID
580:PMID
524:PMID
478:ISBN
349:Smac
255:VEGF
246:IL-7
235:HER2
191:IL-6
149:Axin
147:and
93:IL-2
89:CD28
1234:RTK
1229:Wnt
1128:doi
1087:PMC
1079:doi
1037:PMC
1029:doi
988:doi
947:PMC
939:doi
935:116
893:doi
850:doi
801:doi
763:PMC
755:doi
751:117
713:PMC
705:doi
661:PMC
653:doi
649:117
611:doi
570:PMC
560:doi
514:doi
474:238
386:in
347:of
267:on
175:of
145:APC
77:MHC
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