Sclerotiumrolfsii, a soil borne plant pathogenic fungus secrete a developmental‐stage specific lectin (SRL) which displays strong binding to TF antigen and its derivatives. Histochemical studies revealed specific binding to human cancerous colon tissues but not to normal ones. SRL exhibits strong receptor mediated antiproliferative activity towards human colon cancer cell lines by inducing apoptosis, involving the participation of caspase 8, 9 and 3. It has also been demonstrated that SRL at sub toxic concentrations completely inhibits tumour growth in NOD SCID mice models bearing HT29 xenografts when injected intratumorly. In this study, we investigated the signaling pathways that lead to apoptosis. HT29 cells were treated with lectin and samples were harvested at different time points and gene expression microarray analysis was performed using Agilent’s SurePrint G3 Human Gene Expression 8X60K V2 Microarray kit. Pathway analysis revealed that the MAPK signaling pathway is affected as early as 2h while cell cycle and the DNA damage response pathways are most significantly affected at later time points. Lectin treatment led to immediate over expression of the Jun transcription factor. miRNA expression study of the early time points showed very few miRNAs to be differentially regulated at 2 and 4 h after treatment. However,a significant change in differentially expressed miRNAs was noticed at 12h with the miRNA target list significantly overlapping with the differential gene expression list. The study suggests that the interaction of SRL with HT29 cells triggers apoptosis in these cancer cells by affecting the cell cycle pathway and concurrently inducing DNA damage. The observed effects are ,initiated through the activation of MAP kinase pathway and mediated by the transcription factor JUN. The findings will enable to exploit SRL for its diagnostic potential and also as a targeted drug for cancer therapeutics.