The human homolog of the Drosophila headcase protein slows down cell division of head and neck cancer cells

Abstract

The human homolog of the Drosophila headcase (HECA) belongs to a new class of cell differentiation regulators. In Drosophila, the HECA protein regulates the proliferation and differentiation of cells during adult morphogenesis. There is growing evidence that HECA plays an important role in human carcinogenesis. In different tumor entities, an altered HECA expression was found (colorectal, pancreatic and renal cancer). Colorectal cancer studies also suggested HECA as a marker for early disease stages. Therefore, we speculated whether human HECA affects cell cycle progression and proliferation in head and neck cancer cells. In vivo, we found a distinct HECA protein expression in basal and superficial cells of a healthy oral epithelium via immunohistochemistry, whereas in tissues of oral squamous cell carcinoma (OSCC), a weaker staining was observed, particularly in basal cells. In vitro, mRNA and protein expression analyses of OSCC cell lines exhibited that HECA expression correlates with the state of cellular differentiation. In further investigations, we overexpressed HECA in the OSCC cell line PCI 13 and performed functional assays. HECA-overexpressing OSCC cells revealed a significant extended doubling time (up to 45%, 17 h) and yielded a lower number of proliferating cells (up to 30%) than controls. Flow cytometry analyses have shown that HECA-overexpressing OSCC cells forced to hold in the G(2)/M-Phase. In summary, our results show that human HECA slows down cell division of OSCC cells and may therefore act as a tumor suppressor in head and neck cancer.

Intestinal stem cell ablation reveals differential requirements for survival in response to chemical challenge

“…In addition to a role in preventing cell death, Hdc has been shown to have roles in other biological processes, including tracheal branching and neural development [27][28][29]. Furthermore, the human homolog of hdc , HECA, has been shown to be mis-expressed in certain types of cancer [30][31]. However, a clear molecular function for hdc remains to be elucidated in the fly or in mammalian systems.…”

Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation

“…Evidence has suggested that HECA plays an important role in human carcinogenesis (16). HECA has also previously been found to be related to coronary heart disease, with HECA expression being increased in the atherosclerotic aortic wall (10).…”

Acetazolamide triggers death inducing autophagy in T‐47D breast cancer cells

“…The Q 1 -Q 4 square regions represent cells with following characteristics: Annexin V-FITC À and PI þ (Q 1 ; necrotic cells), Annexin V-FITC þ and PI þ (Q 2 ; late apoptotic cells), Annexin V-FITC À and PI À (Q 3 ; live cells), and Annexin V-FITC þ and PI À (Q 4 ; early apoptotic cells) (Hsu and Yen, 2006;Dowejko et al, 2009;LaPensee et al, 2009). We determined the major cell distribution regions by drawing the common two-dimensional plots of side scattering (SSC) against forward scattering (FSC) without the use of any fluorescent dye.…”

“…The sum of percent values in Q 2 and Q 4 regions was considered as the total percent value for apoptotic cells (early and late apoptotic cells) (Hsu and Yen, 2006;Dowejko et al, 2009;LaPensee et al, 2009). The sum of percent values in Q 2 and Q 4 regions was considered as the total percent value for apoptotic cells (early and late apoptotic cells) (Hsu and Yen, 2006;Dowejko et al, 2009;LaPensee et al, 2009).…”

“…The necessary calculations were next carried out on the four squared regions of Q 1 through Q 4 using the drawn twodimensional plot of Annexin V-FITC against PI. The Q 1 -Q 4 square regions represent cells with following characteristics: Annexin V-FITC À and PI þ (Q 1 ; necrotic cells), Annexin V-FITC þ and PI þ (Q 2 ; late apoptotic cells), Annexin V-FITC À and PI À (Q 3 ; live cells), and Annexin V-FITC þ and PI À (Q 4 ; early apoptotic cells) (Hsu and Yen, 2006;Dowejko et al, 2009;LaPensee et al, 2009).…”