PIK3CA Is Critical for the Proliferation, Invasiveness, and Drug Resistance of Human Tongue Carcinoma Cells

Abstract

PIK3CA is an oncogene component of phosphatidylinositol 3-kinase (PI3K) signaling pathway and is associated with cell proliferation and carcinogenesis in a variety of human cancers. PIK3CA mutation is correlated with the aggressiveness of many epithelial cancers. And so PIK3CA is considered as a major oncogene in many human epithelial malignancies. However, its role in tongue carcinoma is unknown. We used lentiviral-mediated interfering short hairpin RNAs (shRNAs) to knock down PIK3CA expression in tongue carcinoma Tca8113 cells, and then we tested the cell proliferation by MTT assay and cell invasiveness by cell invasion assay. To examine whether PIK3CA is involved in the response of Tca8113 cells to an anticancer drug, cisplatin, we further performed cell death analysis by fluorescence-activated cell sorting (FACS). We found that knocking down PIK3CA led to slower cell growth and lessened cell invasiveness. In addition, PIK3CA downregulation increased Tca8113 cell death after cisplatin treatment, suggesting that PIK3CA downregulation might be helpful to increase the effects of some anticancer drugs. Moreover, in a mouse model of established large sized OSCC, we showed that suppression of PIK3CA markedly diminished tumorigenicity in vivo. To understand its molecular mechanism of action, we measured expression of phospho-PTEN (Ser380) and phospho-AKT (Ser473) by Western blot and found that suppression of PIK3CA inhibited OSCC growth through downregulation of p-PTEN and p-AKT. Our study highlights critical roles for PIK3CA in the tongue cancer, and suggests that PIK3CA gene might be considered as a therapeutic target for clinical tongue cancer.

Clinicopathological Significance of Elevated PIK3CA Expression in Gastric Cancer

“…In an in vitro study using a tongue cancer cell line, inhibition of PIK3CA expression was shown to suppress PTEN and Akt phosphorylations, resulting in decreased proliferative activity and invasiveness and increased drug sensitivity. 22 In gastric cancer cell lines, knockdown of PIK3CA by siRNA also led to reduced tumor cell invasion and migration, suggesting that PIK3CA expression is involved in cancer cell invasion. 23 In this study, we found that PIK3CA upregulation was associated with tumor cell invasion.…”

Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

“…Studies have revealed that PIK3CA and PTEN have an important role in the occurrence and development of OSCC (23)(24)(25)(26)(27)(28)(29)(30)(31). PIK3CA is the key molecule in the PI3K/AKT signaling pathway (40), while PTEN is the most important negative regulatory component in the PI3K/AKT signaling pathway (41).…”

“…At present, there is no clear opinion regarding the associations between PER2 expression changes and the occurrence, development and survival outcomes of OSCC. It has been shown that the development of OSCC is closely related to expression changes of several important tumor-related genes, such as PIK3CA, PTEN, P53, P14ARF and caspase-8 (28)(29)(30)(31)(32)(33)(34). However, it is unclear whether there is any correlation between PER2 expression and the aberrant expression of these tumor-related genes.…”

Immunosuppressive Signaling Pathways as Targeted Cancer Therapies

“…Angiogenic factors such as VEGF-1 have been shown to activate the PI3K pathway preferably in collaboration with PLCγ to promote cancer progression and migration [144] (Figure 7). The other component of the PI3K signaling pathway is PI3KCA which is correlated with cancer progression and drug resistance in the tongue [145] and breast cancers [146]. In an effort to develop combinatorial therapies to decipher drug resistance, Gupta et al investigated the use of KIT/PI3K/MAPK (KPM) pathways as potential targeted therapy for gastrointestinal stromal tumors (GIST).…”