2015
DOI: 10.1007/s13277-015-4385-z
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STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment

Abstract: Uterine cervix cancer is the second most common malignancy in women worldwide with human papillomavirus (HPV) as the etiologic factor. The two main histological variants, squamous cell carcinomas (SCC) and adenocarcinomas (AC), resemble the cell morphology of exocervix and endocervix, respectively. Cancer metabolism is a cancer hallmark conditioned by the microenvironment. As uterine cervix homeostasis is dependent on lactate, we hypothesized lactate plays a role in uterine cervix cancer progression. Using in … Show more

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Cited by 21 publications
(10 citation statements)
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“…Previous reports have indicated that STAT3 increases HIF-1α protein stability and interacts with HIF-1α target gene promoters [62]. Other reports have also shown that activation of STAT3 is involved in the modulation of expression of pH-regulating proteins, CA9 and MCT4 [63]. The present study revealed that acetyl-STAT3 was activated in response to hypoxia, and inhibition of STAT3 decreased hypoxia-induced MCT4 and HIF-1α expression ( Figure 6D,E).…”
Section: Discussionsupporting
confidence: 74%
“…Previous reports have indicated that STAT3 increases HIF-1α protein stability and interacts with HIF-1α target gene promoters [62]. Other reports have also shown that activation of STAT3 is involved in the modulation of expression of pH-regulating proteins, CA9 and MCT4 [63]. The present study revealed that acetyl-STAT3 was activated in response to hypoxia, and inhibition of STAT3 decreased hypoxia-induced MCT4 and HIF-1α expression ( Figure 6D,E).…”
Section: Discussionsupporting
confidence: 74%
“…Monocarboxylate transporters are essential for lactate import and export. In cancer context MCT1 is described as being expressed in cells that preferentially import and consume lactate whereas MCT4 is more prone to export lactate [ 12 ]. Although a report in glycolytic cells from brain tumors has described MCT1 as a mediator of lactate export [ 18 ].…”
Section: Resultsmentioning
confidence: 99%
“…Metabolic adaptation involves an orchestrated remodelling of metabolic intervenients and in lactate metabolism the most important elements are monocarboxylate transporters (MCTs) [ 9 , 10 ] - in cancer MCT1 and MCT4 seem to be the most relevant [ 11 , 12 , 39 ]; and lactate dehydrogenases (LDH), which are able to convert lactate and pyruvate in both ways and have even been considered as putative therapeutic targets in cancer [ 40 , 41 ]. HL60 reacted to lactate and VEGF by increasing MCT1 levels and THP1 expresses high levels of MCT1, which are maintained upon lactate and VEGF exposure (Figure 3A and 3C ).…”
Section: Discussionmentioning
confidence: 99%
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