HIF1A (Human) ELISA Kit

Background: Klotho (KL) was originally characterized as an aging suppressor gene, and has been identified as a tumor suppressor gene in a variety of cancers, including colorectal cancer. Recent years have witnessed the importance of metabolism transformation in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. Our previous studies demonstrated that KL played negative roles in colon cancer cell proliferation and metastasis. However, its role in the cancer cell reprogramming has seldom been reported. The aim of this study was to examine the role of KL in aerobic glycolysis in colorectal cancer. Methods: Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we analyzed the correlation between SUVmax and KL expression in colorectal cancer tissues. The impact of KL on glucose metabolism and its mechanisms were further validated in vitro and in vivo. Results: Patients with lower KL expression exhibited higher F-18-FDG uptake (P < 0.05), indicating that KL might participate in aerobic glycolysis regulation. In vitro assay by using colon cancer cell lines further supported this observation. By overexpressing KL in HTC116 and SW480 cells, we observed that the glycolysis was inhibited and the mitochondrial respiration increased, indicating that KL was a negative regulator of aerobic glycolysis. To seek for the underlying mechanisms, we tried to dig out the relation between KL and HIF1 alpha signaling pathway, and found that KL negatively regulated HIF1a protein level and transcriptional activity. Western blot analysis showed that KL overexpression negatively regulated ERK pathway, and KL regulated aerobic glycolysis in part through its regulation of ERK/HIF1 alpha axis. Conclusions: Taken together, KL is a negative regulator of aerobic glycolysis and KL inhibited glucose metabolism transformation via the ERK/HIF1 alpha axis.

Purpose: Oxygen and glucose deprivation is a common feature of the solid tumor. Regulatory network underlying the adaptation of cancer cells to the harsh microenvironment remains unclear. We determined the mechanistic role of LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1) in cancer cell survival under oxygen-glucose deprivation conditions. Experimental Design: The expression level of LIMS1 was determined by IHC staining and analyzing the mRNA expression profiles from The Cancer Genome Atlas of three human solid tumors. Roles of LIMS1 in cancer cell metabolism and growth were determined by molecular and cell biology methods. A jetPEI nanocarrier was used as the vehicle for anti-LIMS1 siRNAs in mouse models of cancer therapeutics. Results: LIMS1 expression was drastically elevated in pancreatic ductal adenocarcinoma (PDAC). High LIMS1 level was associated with advanced TNM stage and poor prognosis of patients with tumor. Increased LIMS1 expression was pivotal for tumor cells to survive in the oxygenglucose deprivation conditions. Mechanistically, LIMS1 enhanced GLUT1 expression and membrane translocation, which facilitated tumor cell adaptation to the glucose deprivation stress. Furthermore, LIMS1 promoted HIF1A protein translation by activating AKT/mTOR signaling, while hypoxia-inducible factor 1 (HIF1) transactivated LIMS1 transcription, thus forming a positive feedback loop in PDAC cell adaptation to oxygen deprivation stress. Inhibition of LIMS1 with jetPEI nanocarrier-delivered anti-LIMS1 siRNAs significantly increased cell death and suppressed tumor growth. Conclusions: LIMS1 promotes pancreatic cancer cell survival under oxygen-glucose deprivation conditions by activating AKT/mTOR signaling and enhancing HIF1A protein translation. LIMS1 is crucial for tumor adaptation to oxygenglucose deprivation conditions and is a promising therapeutic target for cancer treatment.