Knockdown of pyruvate kinase M2 suppresses bladder cancer progression

نویسندگان

چکیده

Abstract Objectives Bladder cancer (BCa) is one of the most frequently diagnosed cancers urinary tract and has a high mortality. The M2 splice isoform pyruvate kinase (PKM2) key regulator Warburg effect in cells. This study aimed to evaluate metabolic alterations biological behaviours after knocking down PKM2. Methods In this study, 36 pairs BCa tissues adjacent normal were collected analyse expression level PKM2 explore relationship between tumour patient status. After knockdown T24 cells, cell survival, migration, invasion, glucose uptake, lactate production, apoptosis detected. tumour-forming ability PKM2-reducing cells was examined vivo . Results results showed that correlates with stage grade. decreases consumption production suppresses proliferation, invasion while increasing reactive oxygen species levels vitro nude mouse models, reduced xenograft orthotopic size. Moreover, decreased vimentin fibronectin increased E-cadherin expression. Analysis high-throughput sequencing data revealed may also be associated processes diseases. Conclusions Overall, these indicate therapeutic target for patients.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Inhibition of Pyruvate Kinase M2 Markedly Reduces Chemoresistance of Advanced Bladder Cancer to Cisplatin

Chemoresistance to cisplatin is a principal cause of treatment failure and mortality of advanced bladder cancer (BC). The underlying mechanisms remain unclear, which hinders the development of preventive strategies. Recent data indicate that pyruvate kinase M2 (PKM2), a glycolytic enzyme for Warburg effect, is strongly upregulated in BC. This study explores the role of PKM2 in chemoresistance a...

متن کامل

A Novel Pyruvate Kinase M2 Activator Compound that Suppresses Lung Cancer Cell Viability under Hypoxia

Pyruvate kinase M2 isoform (PKM2), a rate-limiting enzyme in the final step of glycolysis, is known to be associated with the metabolic rewiring of cancer cells, and considered an important cancer therapeutic target. Herein, we report a novel PKM2 activator, PA-12, which was identified via the molecular docking-based virtual screening. We demonstrate that PA-12 stimulates the pyruvate kinase ac...

متن کامل

Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit Cancer

Cancer cells rewire metabolism to meet biosynthetic and energetic demands. The characteristic increase in glycolysis, i.e., Warburg effect, now considered as a hallmark, supports cancer in various ways. To attain such metabolic reshuffle, cancer cells preferentially re-express the M2 isoform of pyruvate kinase (PKM2, M2-PK) and alter its quaternary structure to generate less-active PKM2 dimers....

متن کامل

Nuclear Pyruvate Kinase M2 Functional Study in Cancer Cells

Cancer cells take more glucose to provide energy and phosphoryl intermediates for cancer progression. Meanwhile, energy-provider function of mitochondria in cancer cells is disrupted. This phenomenon is so-called Warburg effect, which is discovered over eighty years ago. The detail mechanisms for Warburg effect are not well defined. How glycolytic enzymes contribute to cancer progression is not...

متن کامل

Tumour M2-pyruvate kinase: a gastrointestinal cancer marker.

BACKGROUND Gastrointestinal cancer tumour markers are valuable in the detection of recurrence following resection or in monitoring response to chemotherapy. CEA, CA19-9, CA-50 and CA72-4 are currently available but are nonspecific and have a low sensitivity. 'Tumour M2-pyruvate kinase' was described by Eigenbrodt around 1985. In cancers the active tetrameric form of the M2 isoenzyme of pyruvate...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Oncologie

سال: 2023

ISSN: ['1765-2839', '1292-3818']

DOI: https://doi.org/10.1515/oncologie-2023-0014