Opposite effects of tumor protein D (TPD) 52 and TPD54 on oral squamous cell carcinoma cells

Abstract

The tumor protein D52 (TPD52) protein family includes TPD52, -53, -54 and -55. Several reports have shown important roles for TPD52 and TPD53, and have also suggested the potential involvement of TPD54, in D52-family physiological effects. Therefore, we performed detailed expression analysis of TPD52 family proteins in oral squamous cell carcinoma (OSCC). Towards this end, TPD54-overexpressing or knocked-down cells were constructed using OSCC-derived SAS, HSC2 and HSC3 cells. tpd52 or tpd53 was expressed or co-expressed in these cells by transfection. The cells were then analyzed using cell viability (MTT), colony formation, migration, and invasion assays. In OSCC-xenograft experiments, the cells were transplanted into nude mice together with injection of anti-tpd siRNAs. MTT assay of cell monolayers showed little differences in growth of the transfected cells. tpd54 overexpression in SAS cells significantly decreased colony formation in an anchorage-independent manner. Additionally, knock-down of tpd54 enhanced the number of colonies formed and overexpression of tpd52 in tpd54 knock-down cells increased the size of the colonies formed. The chemotaxis assay showed that tpd54 overexpression decreased cell migration. In the OSCC-xenograft in vivo study, tpd54 overexpression slightly attenuated tumor volume in vivo, despite the fact that tumor metastasis or cell survival was not involved. Our results showed that TPD54 not only downregulated anchorage-independent growth and cell migration in vitro, but also attenuated tumor growth in vivo. Based on these results, it is considered that TPD54 might act as a negative regulator of tumor progression in OSCC cells.

The novel function of tumor protein D54 in regulating pyruvate dehydrogenase and metformin cytotoxicity in breast cancer

“…Studies are limited with regard to the biological function of TPD54 in cancer cells, especially in breast cancer. In oral squamous cell carcinoma cells, TPD54 was reported to be a negative regulator of tumor progression by downregulating anchorage-independent cell growth and migration in vitro and by attenuating tumor growth in vivo [12]. Our data demonstrate that, in breast cancer cells, downregulation of TPD54 can reduce cellular oxygen consumption, increase colony formation, and decrease cancer cell sensitivity to metformin treatment.…”

“…Recent studies have also shown that TPD54 affects cell proliferation, cell adhesion, and invasion [11]. Furthermore, TPD54 has been shown to have opposite effects to TPD52 in oral squamous cell carcinoma (OSCC) by preventing colony formation and cell migration [12]. However, the underlying mechanisms of TPD54’s role in cancer, including breast cancer, remain unclear.…”

Tumor Protein D52 Is Upregulated in Oral Squamous Carcinoma Cells Under Hypoxia in a Hypoxia-inducible-factor-independent Manner and Is Involved in Cell Death Resistance

“…Shang et al [21] showed that the expression of PC-1/PrLZ, a splicing variant of human TPD52, is increased by stress from irradiation. Moreover, we revealed that TPD52 is strongly expressed at the center of OSCC tissue and plays an important role in OSCC cell growth [19]. Another report of ours represented that TPD52 is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein (TIAR) via mRNA stability [22].…”

“…Resected specimens were xed with 10% formalin, embedded in para n, stained with hematoxylin and eosin (H-E) (Sakura Finetek Japan, Tokyo, Japan), and then immunohistochemically stained for p62, Akt, and phospho-Akt, as described previously [19].…”

“…Other family members, such as TPD53 (also known as TPD52L1), TPD54 (TPD52L2), and TPD55 (TPD52L3), have been reported to be highly expressed in ovary [9][10][11], testis [12,14], colon [15,16], and prostate cancer [2,15], as well as in brain tumors [16], lymphoma [17], and leukemias [17,18]. We reported that TPD54 is a negative regulator of extracellular-matrixdependent migration and cell attachment in oral squamous carcinoma cells [19]. Among the family members, TPD52 has been studied the most, due to its role in the malignancy of various cancer cells.…”