自噬相關蛋白酶4BATG4B)是自噬作用中不可少的蛋白酶,Ser383/392處磷酸化的ATG4B可增加其蛋白水解活性。 ATG4B的表現和活化對於癌細胞的增殖和侵襲相當重要。然而,ATG4BSer383/392處磷酸化的ATG4BOSCC患者臨床之關聯性仍然未知,尤其在頰黏膜SCCBMSCC)和舌頭SCCTSCC)患者中。使用498OSCC患者檢體做成組織微陣列,包括179BMSCC249TSCC患者,我們發現BMSCCTSCC患者腫瘤組織中的ATG4BSer383/392處磷酸化的ATG4B之蛋白表現量比鄰近組織正常中的要高。在OSCC患者中,特別是在晚期腫瘤患者中,高蛋白表現量的ATG4B與較差的疾病特異性生存率(DSS)有顯著相關。另外,Ser383/392處磷酸化的ATG4B1蛋白表現量與TSCC患者的不良無病生存率(DFS)也相關。此外,在BMSCCTSCC患者中,ATG4B蛋白表達量與Ser383/392處磷酸化ATG4B蛋白表現量呈現正相關。然而,僅在TSCC患者中,同時高蛋白表現量的ATG4BSer383/392處磷酸化的ATG4B與患者較差的DFS相關,而在BMSCCTSCC患者中,它們卻與患者DSS無顯著相關。此外,用反義寡核苷酸(ASO)或干擾RNAsiRNA)沉默ATG4B可以減少TW2.6SAS口腔癌細胞的細胞增殖。另外,剔除口腔癌細胞的ATG4B可以減少細胞遷移和侵襲。綜上所述,這些發現顯示,ATG4B可能作為未來OSCC患者的潛在生物標誌物和治療靶標。

生科 02 劉佩芬 CH口腔鱗狀細胞癌治療的新契機01


生科 02 劉佩芬 CH口腔鱗狀細胞癌治療的新契機02






Cancers 2019, 11(12), 1854



Oral squamous cell carcinoma (OSCC) remains one of the major leading causes of cancer death worldwide due to the lack of potential biomarkers and therapeutic targets. Thus, our research is focusing on identifying potential biomarkers and therapeutic targets for OSCC. We have analyzed the gene expression in the tissues of oral cancer patients from the Cancer Genome Atlas database or performed siRNA library screening to identify potential oncogenes and tumor suppressive genes by comparing gene expression between normal and tumor tissue of OSCC patients with quantitative polymerase chain reaction and immunohistochemistry. We also verified roles and molecular mechanisms of these potential biomarkers by using OSCC cancer cells and xenografted mice models. So far, we have published several related papers with potential OSCC biomarkers and therapeutic targets, as shown in Figure 1. Here, we introduced one of the potential biomarkers and therapeutic targets-autophagy-related protease 4B (ATG4B), as shown in Figure 2.

 Autophagy related protease4B (ATG4B) is an essential protease for the autophagy machinery, and ATG4B phosphorylation at Ser383/392 increases its proteolytic activity. ATG4B expression and activation are crucial for cancer cell proliferation and invasion. However, the clinical relevance of ATG4B and phospho-Ser383/392-ATG4B for OSCC remains unknown, particularly in buccal mucosal SCC(BMSCC) and tongue SCC (TSCC). With a tissue microarray comprising specimens from 498 OSCC patients, including 179 BMSCC and 249 TSCC patients, we found that the protein levels of ATG4B and phospho-Ser383/392-ATG4B were elevated in the tumor tissues of BMSCC and TSCC compared with those in adjacent normal tissues. High protein levels of ATG4B were significantly associated with worse disease-specific survival (DSS) in OSCC patients, particularly in patients with tumors at advanced stages. In contrast, phospho-Ser383/392-ATG4B expression was correlated with poor disease-free survival (DFS) in TSCC patients. Moreover, ATG4B protein expression was positively correlated with phospho-Ser383/392-ATG4B expression in both BMSCC and TSCC. However, high coexpression levels of ATG4B and phospho-Ser383/392-ATG4B were associated with poor DFS only in TSCC patients, whereas they had no significant association with DSS in BMSCC and TSCC patients. In addition, silencing ATG4B with an antisense oligonucleotide (ASO) or small interfering RNA (siRNA) diminished cell proliferation of TW2.6 and SAS oral cancer cells. Further, knockdown of ATG4B reduced cell migration and invasion of oral cancer cells. Taken together, these findings suggest that ATG4B might be a potential biomarker and therapeutic target for OSCC patients in the future.

02 劉佩芬 EN口腔鱗狀細胞癌治療的新契機01


02 劉佩芬 EN口腔鱗狀細胞癌治療的新契機02

Main researcher Intro.

Assistant Professor Dr. Pei-Feng Liu

(Department of Biomedical Science and Environment Biology)

Author Email:


Paper cited from:

Cancers 2019, 11(12), 1854

Research Paper available online on website: