Elevated Soluble Galectin-3 as a Marker of Chemotherapy Efficacy in Breast Cancer Patients: A Prospective Study

Figure 6

Proposed mechanism of action for chemotherapy induced extracellular Gal-3: (a) cells with inactive p53 have low extracellular and high cytoplasmic levels of Gal-3. The cytoplasmic Gal-3 is antiapoptotic through Bcl2 binding at the mitochondrial membrane. Many cancer cells have nonfunctional or partially functional p53 due to direct mutations or mutations in the pathway related to its activation. In addition, a major difference between normal and cancer cells is the presence of aberrantly enhanced glycans on tumor cells. A recent study has found apoptotic response in cancer cells due to secreted Gal-3 binding to β1-integrin with aberrant N-glycosylations [26]. (b) Activation of wt-p53 expression leads to secretion of Gal-3 through transcriptional upregulation of proteins like TSAP6 important for exosome formation [21]. This results in cytoplasmic Gal-3 secretion in the tumor environment with a concomitant decrease in intracellular levels. The secreted Gal-3 binds to β1-integrin with the abnormal glycosylations on same or bystander cell leading to apoptotic response. Lightning bolt represents chemotherapy induced activation of p53.

(a)

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