Role of BMI1, a Stem Cell Factor, in Cancer Recurrence and Chemoresistance: Preclinical and Clinical Evidences

Abstract

There is increasing evidence that a variety of cancers arise from transformation of normal stem cells to cancer stem cells (CSCs). CSCs are thought to sustain cancer progression, invasion, metastasis, and recurrence after therapy. Reports suggest that CSCs are highly resistant to conventional therapy. Emerging evidences show that the chemoresistance of CSCs are in part due to the activation of B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), a stem cell factor, and a polycomb group family member. BMI1 is reported to regulate the proliferation activity of normal, stem, and progenitor cells. BMI1 plays a role in cell cycle, cell immortalization, and senescence. Numerous studies demonstrate that BMI1, which is upregulated in a variety of cancers, has a positive correlation with clinical grade/stage and poor prognosis. Although evidences are in support of the role of BMI1 as a factor in chemoresistance displayed by CSCs, its mechanism of action is not fully understood. In this review, we provide summary of evidences (with mechanism of action established) suggesting the significance of BMI1 in chemoresistance and recurrence of CSCs.

Bmi-1 expression modulates non-small cell lung cancer progression

“…3 B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is an epigenetic chromatin modifier that acts as a key component of PcG proteins, which plays important roles in mammalian stem cell selfrenewal, cellular differentiation and neoplasia. 4 It was initially identified as a proto-oncogene that cooperates with c-myc in generation of B-and T-cell lymphomas. 5,6 Bmi-1 is overexpressed in NSCLC and other epithelial malignancies, including colorectal cancer, liver cancer, breast cancer and nasopharyngeal cancer.…”

Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells

“…The sensitivity to apoptosis of the different cancer cell types is diverse, and it is widely accepted that a subpopulation of malignant cells, so-called cancer stem cells (CSCs), are relatively resistant to cytotoxic agents as compared to the majority of non-stem cancer cells [11]. These CSCs are thought to be responsible for the high incidence of disease recurrence after complete disappearance of a tumor has been achieved with conventional chemotherapy.…”

PLK1 Inhibition Down-regulates Polycomb Group Protein BMI1 via Modulation of the miR-200c/141 Cluster

“…Hence, CSCs are attractive targets for cancer therapy as well as cancer prevention. BMI1, the most well characterized PcG protein is a critical regulator of CSCs (45). The self-renewal of breast, prostate and colorectal CSCs have been shown to be regulated by BMI1 (10,46,47).…”