Expression and clinicopathological significance of lipin‐1 in human breast cancer and its association with p53 tumor suppressor gene

Abstract

Breast cancer (BC) is an important cause of female cancer‐related death. It has recently been demonstrated that metabolic disorders including lipid metabolism are a hallmark of cancer cells. Lipin‐1 is an enzyme that displays phosphatidate phosphatase activity and regulates the rate‐limiting step in the pathway of triglycerides and phospholipids synthesis. The objective of this study was to evaluate lipin‐1 expression, its prognostic significance, and its correlation with p53 tumor suppressor in patients with BC. In this study, 55 pairs of fresh samples of BC and adjacent noncancerous tissue were used to analyze lipin‐1, using quantitative real‐time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other clinicopathological variables and p53 was also examined using IHC technique. The cell migration was studied in MCF‐7 and MDA‐MB231 cells following the inhibition of lipin‐1 by propranolol. Our results show that the relative expression of lipin‐1 messenger RNA was significantly higher in BC tissues compared with the adjacent normal tissue and its inhibition reduced cell migration in cancer cells. This upregulation was negatively correlated with histological grade of tumor and p53 status (p = .001 and p = .034) respectively and positively correlated with the tumor size (p = .006). Our results also seem to indicate that the high lipin‐1 expression is related to a good prognosis in patients with BC. The expression of lipin‐1 may be considered as a novel independent prognostic factor. The inhibition of lipin‐1 may also have therapeutic significance for patients with BC. The correlation between lipin‐1 and p53 confirms the role of p53 in the regulation of lipid metabolism in cancer cells.

Alterations of Lipid Metabolism in Cancer: Implications in Prognosis and Treatment

“…LPIN1 is upregulated in lung adenocarcinoma tumor tissues, and high LPIN1 expression was correlated with poor prognosis of patients with lung adenocarcinoma (134). In breast cancer, previous results seem to indicate that the high LPIN expression is related to a good prognosis (135). However, in basal-like TNBC, high LPIN1 expression correlates with the poor prognosis of these patients (136).…”

The diversity and breadth of cancer cell fatty acid metabolism

“…The increased levels of LPAAT in colorectal cancer [228] would be expected to increase the conversion of lysophosphatidate to phosphatidate. However, LPIN1, one of three members of the LPIN family, is highly expressed in ovarian cancer [232], hepatocellular carcinoma [233], and breast cancer [234,235], and therefore causing an increased conversion of phosphatidate to DG and resulting in no accumulation of PA. Knockdown of LPIN1 reduced incorporation of extracellular palmitate into glycerophospholipids, indicating reduced synthesis and remodeling, which resulted in impaired basal-like triple-negative breast cancer cell viability and orthotopic xenograft growth [234]. This suggests that enhanced conversion of phosphatidate into DG would be advantageous.…”

“…The final lipid we will discuss in the glycero(phospho)lipid synthesis pathway is DG, which is regulated by LPIN, DGK, and DGAT enzymes, as well as PLCs which de-phosphorylate glycerophospholipids (see review [243]). The reported increased expression of DGK in cancer cells should cause a reduction in DG levels [236][237][238]; the increase in LPIN levels predicts an increase in DG [232][233][234][235]. To complicate our understanding of DG metabolism in cancer, both DGAT isoforms, DGAT1 and DGAT2 that encoded by genes that belong to two distinct gene families [244], are highly expressed in a range of cancers and is associated with increased TG levels and lipid droplet abundance [245,246].…”

Interleukin‑18 and ‑10 may be associated with lymph node metastasis in breast cancer

“…The two scores were multiplied to obtain a final score, based on which the positivity of IL-18 in the section was assessed according to the following criteria: 3 points, (1+); 4-5 points, (2+); and 6-9 points, (3+). The sections with a total IL-18 score of ≤2 points were considered to be IL-18-negative (23,24).…”