Definition: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
Input: Context: In advanced cancer, including glioblastoma, the TGF pathway acts as an oncogenic factor. Some tumors exhibit aberrantly high TGF activity, and the mechanisms underlying this phenomenon are not well understood. We have observed that TGF can induce TGF2, generating an autocrine loop leading to aberrantly high levels of TGF2. We identified cAMP-responsive element-binding protein 1 (CREB1) as the critical mediator of the induction of TGF2 by TGF. CREB1 binds to the TGFB2 gene promoter in cooperation with SMAD3 and is required for TGF to activate transcription. Moreover, the PI3K-AKT and RSK pathways regulate the TGF2 autocrine loop through CREB1. The levels of CREB1 and active phosphorylated CREB1 correlate with TGF2 in glioblastoma. In addition, using patient-derived in vivo models of glioblastoma, we found that CREB1 levels determine the expression of TGF2. Our results show that CREB1 can be considered a biomarker to stratify patients for anti-TGF treatments and a therapeutic target in glioblastoma.
Answer: TGF is considered a promising therapeutic target, and several clinical trials using TGF inhibitors are generating encouraging results. Here, we discerned the molecular mechanisms responsible for the aberrantly high levels of TGF2 found in certain tumors, and we propose biomarkers to predict the clinical response to anti-TGF therapies.
Output:
Does active CREB1 promote a malignant TGF2 autocrine loop in glioblastoma?