Correction: Pan et al. Impact of FAK Expression on the Cytotoxic Effects of CIK Therapy in Triple-Negative Breast Cancer. Cancers 2020, 12, 94.

In the original article [...].

The CDK6-c-Jun-Sp1-MMP-2 axis as a biomarker and therapeutic target for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has high metastatic, drug-resistance, and recurrence rates, and is characterized by an angiogenic and fibrotic microenvironment that favors cancer malignancy. However, details of the mechanisms underlying malignancy are still largely unknown. Our mouse model indicated that knockdown of CDK6 inhibited lung metastasis significantly compared to parental cells. Immunohistochemical analyses revealed that the levels of collagen and the angiogenic marker matrix metalloproteinase (MMP)-2 were much lower in CDK6-deficient cells. To examine mechanisms in the CDK6-mediated phenotype of cancer cells, we studied its role in MMP-2 expression. CDK6 mediated the recruitment of transcription factors including c-Jun and Sp1 to the MMP2 promoter. Knockdown of CDK6 significantly suppressed the expression of MMP2 mRNA. Consistent with the in vitro data, the expression of CDK6 was positively correlated with the angiogenic and fibrotic tumor microenvironment in TNBC patient tissues as shown by MMP-2 and fibronectin staining, respectively. More importantly, after screening a small molecule library of 31 protein kinase inhibitors, we found that the Raf inhibitor sorafenib displayed the highest cytotoxicity in CDK6-depleted cells. These data indicate that CDK6 serves as an anti-microenvironment target and affects the drug response in retinoblastoma-proficient TNBC, suggesting that combining a CDK6 inhibitor and sorafenib leads to a synthetic effect that may represent a personalized therapeutic approach for patients with TNBC.

Impact of BMI1 expression on the apoptotic effect of paclitaxel in colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Despite advances in treatment, no treatment modality specific for the different CRC phenotypes has been developed. BMI1 has been previously reported to play an important role in the regulation of cancer stem cells and cell cycle in CRC. However, the role of BMI1 in individualized treatment for CRC is largely unknown. In this study, we found that the apoptotic effect of paclitaxel is more profound in BMI1-depleted cells. The apoptotic effect is exerted by promoting caspase-8-independent apoptotic pathways after combination with paclitaxel in BMI1 knockdown cells. This effect could be totally recovered by pretreatment with caspase inhibitor compared with caspase-8 inhibitor alone. It has been reported that the levels of MCL-1 play a role in regulating cell resistance to paclitaxel treatment. Our data indicated that the downregulation of MCL-1 through the activation of GSK3beta and JNK is driven by BMI1 depletion. Consistent with in vitro data, a synergic anti-growth effect of BMI1 depletion with paclitaxel treatment was shown in vivo. In conclusion, paclitaxel has a stronger suppressive effect on tumor growth and proliferation in CRC with low BMI1 expression. Thus, in CRC patients, paclitaxel could be specifically indicated for patients with low BMI1 expression.

[LIN Guo-hua's experience in treating dry eye syndrome with Lingnan fire needling].

Professor LIN Guo-hua is the representative inheritor of Lingnan fire needling therapy. He proposed that the clinical application of Lingnan fire needling is mainly based on pattern differentiation according to eight priciples, as well as in coordination with the theories of meridians and zang-fu organs. He believes that dry eye syndrome can be treated from the aspects of deficiency of liver and kidney, heart yin deficiency, and qi and yin deficiency. Through deeply digging the connotation of ancient classics, and combined his clinical practice using Lingnan fire needling, professor LIN created a unique therapy that select "Neichengqi"as the main acupoint combined with Xialeidian, Dagukong (EX-UE 5), Xiaogukong (EX-UE 6) and Shaoze (SI 1) in the treatment of dry eye syndrome. In this paper, from the etiology and pathogenesis of dry eye syndrome and therapeutic characteristics of Lingnan fire needling, the thoughts of syndrome differentiation and characteristics of acupoints selection of professor LIN were analyzed by a typical case, and it is expect to enrich the clinical treatment plan for dry eye syndrome.

Impact of FAK Expression on the Cytotoxic Effects of CIK Therapy in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer in which several common diagnostic biomarkers are lost. Due to the loss of expression of receptors, treatment options for TNBC are limited. Therefore, finding safe and effective treatments for patients with TNBC is a major objective for clinicians. Previous studies suggested that cytokine-induced killer (CIK) cells may be beneficial for patients with a variety of tumor types. However, CIK therapy is not effective for all patients. In this study, we found that focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase that regulates several cellular functions in different cells, has the potential to regulate tumor cells sensitized to CIK cells. Knockdown of FAK expression in TNBC cells or the treatment of TNBC cells with a FAK inhibitor followed by coculture with CIK cells increases death of TNBC cells, suggesting that FAK plays important roles in sensitizing tumor cells to CIK cells. This phenomenon could be regulated by a FAK-programmed death-ligand 1 (PD-L1)-related mechanism. Overall, our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment, and show that CIK cell therapy combined with FAK inhibitors may be a novel therapeutic strategy for patients with TNBC.

miR-124 inhibits growth and invasion of gastric cancer by targeting ROCK1.

MicroRNAs (miRNAs) act as critical regulators of genes involved in many biological processes. Aberrant alteration of miRNAs have been found in many cancers, including gastric cancer (GC), but the molecular mechanisms are not well understood. Herein, we investigated the role of miR-124 in GC. We found that its expression was significantly reduced in both GC tissue samples and cell lines. Forced expression of miR-124 suppressed GC cell proliferation, migration, and invasion. Furthermore, the Rho-associated protein kinase (ROCK1) was identified as a direct target of miR-124 in GC cells. Finally, silencing of ROCK1 showed similar effects as miR-124 overexpression, while supplementation of ROCK1 remarkably restored the cell growth and invasion inhibited by miR-124. Together, our data demonstrate that miR-124 acts as a tumor suppressor by targeting ROCK1, and posit miR-124 as a novel strategy for GC treatment.