ArticleAmerican journal of cancer research2021
Obesity-associated leptin promotes chemoresistance in colorectal cancer through YAP-dependent AXL upregulation.
Article in American journal of cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk.GeroScience · 2025Pooled it
- The emerging role of the Hippo signaling pathway in interorgan crosstalk.The FEBS journal · 2026Review
- Leptin Signaling at the Crossroads of Obesity, Immunity, and Cancer: Mechanistic Insights and Therapeutic Implications.Biomolecules & therapeutics · 2026Review
- Adipocytes as Orchestrators of Multimodal Cancer Therapy Resistance.Biomolecules & therapeutics · 2026Review
- Crosstalk Between Leptin and Adiponectin in Colorectal Cancer: Molecular Mechanisms and Oncogenic Pathways.International journal of molecular sciences · 2026Review
- Integrated serum metabolomics reveal molecular mechanism of Xietu Hemu prescription on metabolic dysfunction-associated steatotic liver disease-related obesity.World journal of hepatology · 2025Article
- Regulatory roles of non-coding and exosomal RNAs in colorectal cancer: spotlight on angiogenesis.Clinical and experimental medicine · 2025Review
- Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.World journal of gastrointestinal oncology · 2024Article
- MiR-34a functions as a tumor suppressor in oral cancer through the inhibition of the Axl/Akt/GSK-3β pathway.Journal of dental sciences · 2024Article
- Nuclear translocation of Axl contributes to the malignancy of oral cancer cells.Journal of dental sciences · 2024Article
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
- [Obesity and Colorectal Cancer].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2023Review
- Review
- GAS6/Axl is associated with AMPK activation and attenuates HApoptosis : an international journal on programmed cell death · 2023Article
- The Potential Chemopreventive Effect ofInternational journal of molecular sciences · 2023Article
- Hsa_hsa_circ_0081069 promotes the progression of colorectal cancer through sponging miR-665 and regulating E2F3 expression.Journal of clinical laboratory analysis · 2022Article
- Insulin and cancer: a tangled web.The Biochemical journal · 2022Review
- YAP1 activation and Hippo pathway signaling in the pathogenesis and treatment of intrahepatic cholangiocarcinoma.Advances in cancer research · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity results from an imbalance between caloric intake and energy expenditure, and it is highly associated with colorectal carcinogenesis and therapeutic resistance in patients with colorectal cancer (CRC). Dysregulation of adipokine production in obesity has been reported to cause malignant behaviors in CRC. Leptin, which is the principal hormone secreted by adipocytes and an obesity-associated adipokine, is significantly overexpressed in CRC tissues. However, the effect of leptin on chemoresistance in CRC is unclear. Therefore, the aim of this study was to clarify the role of leptin and the underlying mechanisms in mediating 5-fluorouracil (5-FU) resistance in CRC. We used palmitate to artificially generate obese adipocytes. As expected, lipid accumulation was significantly increased in obese adipocytes. We demonstrated that CRC cells incubated with conditioned media (CM) harvested from obese adipocytes were associated with increased resistance to 5-FU. Notably, this increase in resistance to 5-FU was through the elevated production and secretion of leptin. Leptin could further stimulate the expression of AXL and activate its downstream signaling molecule, PLCγ, thereby resulting in an increased expression of p-glycoprotein (P-gp) in CRC cells. Mechanistically, leptin induced AXL expression via the inhibition of AMPK and subsequent increase in YAP activation and nuclear translocation. In addition, nuclear YAP interacted with TEAD and promoted the occupancy of TEAD on the AXL promoter, thereby stimulating AXL promoter activity after leptin treatment. Furthermore, leptin neutralization rescued the sensitivity of CRC tumors to 5-FU in mice fed on a high-fat diet (HFD). These results indicated that leptin mediated 5-FU resistance through YAP-dependent AXL overexpression in CRC.
Indexed as
Identifiers
34659884PMC8493400W3205174435What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.