Knockdown of Microtubule Associated Serine/threonine Kinase Like Expression Inhibits Gastric Cancer Cell Growth and Induces Apoptosis by Activation of ERK1/2 and Inactivation of NF-κB Signaling

Abstract

SummaryMicrotubule-associated serine/threonine kinase (MASTL) functions to regulate chromosome condensation and mitotic progression. Therefore, aberrant MASTL expression is commonly implicated in various human cancers. This study analyzed MASTL expression in gastric cancer vs. adjacent normal tissue for elucidating the association with clinicopathological data from patients. This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro. The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN, GEPIA, and Oncomine online databases. Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells. RT-qPCR, Western blotting, cell viability, cell counting, flow cytometric apoptosis and cell cycle, and colony formation assays were performed. MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue, and the MASTL expression was associated with advanced tumor stage, Helicobacter pylori infection and histological subtypes. On the other hand, knockdown of MASTL expression significantly reduced tumor cell viability and proliferation, and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis. At protein level, knockdown of MASTL expression enhanced levels of cleaved PARP1, cleaved caspase-3, Bax and p-ERK1/2 expression, but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells. MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression, whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis. Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.

Therapeutic natural compounds Enzastaurin and Palbociclib inhibits MASTL kinase activity preventing breast cancer cell proliferation

“…Studies investigated MASTL to be an important drug target for anticancer treatment due to its multifarious roles such as cellular transformation, metastasis, chromosomal instability, and the DNA damage response in various cancers [10,11,24]. MASTL is reported to be upregulated in several cancer cell lines including breast cancer cells [4,[25][26][27].…”

Role of immune escape in different digestive tumours

“…Another common immunosuppressive molecule, NF-κB, is widely found in tumour cells of the digestive system and participates in immune escape mainly by affecting the function of T cells. In a study on the effect of microtubule-associated serine/threonine kinase (MAST1) on gastric malignant tumours, it was found that tumour cells after MAST1 gene knockout exerted an antitumour effect by downregulating the expression of NF-κB p65, suggesting that NF-κB may be involved in the immune escape of tumour cells[ 79 , 80 ]. NF-κB1 p50 (hereinafter referred to as p50) realizes the immune escape of tumour cells by affecting the transcription of effector T cells at the cellular transcriptional level[ 81 , 82 ].…”