Fructose-1,6-bisphosphatase-1 decrease may promote carcinogenesis and chemoresistance in cervical cancer

Abstract

Fructose-1,6-bisphosphatase-1 (FBP1), a gluconeogenesis rate-limiting enzyme expressed in various tissues, is important in the carcinogenesis of various cancers. To evaluate the association of FBP1 expression and carcinogenesis and chemoresistance in cervical cancer, the present study analyzed 140 patients of squamous cell carcinoma of cervical cancer (CSCC) who had adjuvant concurrent chemoradiation therapy following radical surgery. By detecting FBP1 protein expression in paraffin‑embedded tumor tissues through immunohistochemistry, it was observed that 50% of the cases had a low expression of FBP1, which was associated with a shorter overall survival time (P=0.011). In addition, FBP1 mRNA level was downregulated in tumor tissues, compared with cervical normal tissues. Among the tumor‑associated prognostic factors, loss of FBP1 expression (χ2‑test, P=0.025) was significantly associated with the tumor recurrence and greater tumor stage of cervical cancer patients (2‑test, P<0.0001). In 3‑(4,5)‑dimethylthiahiazo(‑z‑y1)-3,5-diphenytetrazoliumromide (MTT) assay of primary tumor cells, the median in vitro inhibition rate of cisplatin, carboplatin, nedaplatin, and oxaliplatin was 62, 47, 58 and 52%, respectively. Although there was no significant association between FBP1 expression and in vitro tumor inhibition rates of primary tumor cells, overexpression of FBP1 markedly suppressed carcinogenesis and restored the chemosensitivity to cisplatin in cervical cancer cell lines of HeLa and CaSki. Overall, decreased levels of FBP1 may be used as a predictor for poor prognosis of cervical cancer patients, however the mechanism requires further investigation.

Metabolic Symbiosis in Chemoresistance: Refocusing the Role of Aerobic Glycolysis

“…Compared with normal tissues, FBP1 mRNA levels were significantly decreased in cervical cancer cells, and the downregulation of FBP1 expression was closely related to tumor recurrence and tumor stage in cervical cancer patients. Experiments validated that the overexpression of FBP1 significantly inhibits tumor cell growth and restores the chemosensitivity of cervical cancer cells by suppressing the glycolytic process (60). Gemcitabine, a first-line treatment for pancreatic cancer, is a drug that cancer cells often develop a resistance to.…”

Gluconeogenesis in cancer cells – Repurposing of a starvation-induced metabolic pathway?

“…Low expression associated with poor survival in breast cancer [72], gastric cancer [81], pancreatic cancer [73], NSCLC [75], and cervical carcinoma patients [85]…”

“…Overexpression reduces/silencing enhances proliferation in breast cancer [72], cholangiocarcinoma [83], cervical carcinoma [85], pancreatic cancer [73,74] and colon carcinoma cells [86]…”

Genetic Manipulation of FBP1 Expression in Breast Cancer Cells Reveals the Potential of FBP1 to Disrupt The Warburg Effect, and Nutrient Mediated Adaptive Post-Translational Regulation of FBP1 Protein Levels.

“…Recent years have seen a surge in research exploring the relevance of gluconeogenesis and the key enzyme fructose-1,6-bis-phosphatase FBP1 in cancer contexts [1][2][3][4][5]. The epigenetic silencing of FBP1 has been observed in several types of tumours and linked to poorer prognoses [2,3,[5][6][7][8][9]. For many cancers, the loss of FBP1 has been described as an advantageous event in the metabolic rewiring towards aerobic glycolysis.…”

“…Breast tumours with better survival rates show positive FBP1 expression, while the more advanced forms of basal-like, triple-negative and metastatic breast cancer lack FBP1 expression. [9,10]. This heterogeneity of breast cancers in regard to FBP1 expression makes breast cancer cells an apt model to further investigate the effects and regulation of FBP1 in contexts of cancer.…”